氏名

ツツイ カズヨシ

筒井 和義

職名

教授

所属

(教育学部)

連絡先

メールアドレス

メールアドレス
k-tsutsui@waseda.jp

住所・電話番号・fax番号

住所
〒162-8480新宿区 若松町2-2
電話番号
03-5369-7311
fax番号
03-3355-0316

URL等

WebページURL

http://www.f.waseda.jp/k-tsutsui

研究者番号
20163842

本属以外の学内所属

兼担

理工学術院(大学院先進理工学研究科)

商学学術院(商学部)

研究院(研究機関)/附属機関・学校(グローバルエデュケーションセンター)

学内研究所等

ライフサポートイノベーション研究所

研究所員 2014年-2014年

ライフサポートイノベーション研究所

研究所員 2015年-

学際融合脳科学研究所

研究所員 2018年-

理工学術院総合研究所(理工学研究所)

兼任研究員 2006年-2018年

理工学術院総合研究所(理工学研究所)

兼任研究員 2018年-

学歴・学位

学歴

-1976年 早稲田大学 教育学部 生物学
-1981年 早稲田大学 理工学研究科 応用物理学

学位

理学博士 課程 早稲田大学 形態・構造

経歴

2006年-早稲田大学 教育・総合科学学術院 統合脳科学研究室 教授
2005年-2006年早稲田大学 大学院理工学研究科 客員教授
2003年-2006年広島大学統合脳科学プロジェクト研究センター センター長
2000年-財団法人サントリー生物有機科学研究所アドバイザー
1996年-2006年広島大学総合科学部 教授
1993年-1996年広島大学総合科学部 助教授
1991年-1993年神戸大学医学部 講師
1988年-ワシントン大学(米国) 動物学教室 客員研究員
(併任)
1988年-1989年南カリフォルニア大学(米国) 神経生物学教室 客員研究員(併任)

所属学協会

国際神経ペプチド学会日本支部 幹事

国際鳥類学会連合 日本代表

国際両生類爬虫類内分泌学・神経科学会議 評議員

国際比較内分泌学会 評議員

アジアオセアニア比較内分泌学会 会長

日本比較内分泌学会 会長

国際鳥類内分泌会議 会長

ニューロエソロジー談話会 世話人

日本下垂体研究会 会長

日本比較生理生化学会 評議員

日本鳥類内分泌研究会 代表世話人

日本動物学会 理事

委員歴・役員歴(学外)

"FrontiersinExperimentalEndocrinology"AssociateEditor、
"FrontiersinNeuroendocrineScience"AssociateEditor、
"GeneralandComparativeEndocrinology"Editor、
"JournalofNeuroendocrinology"EditorialBoardMember、
"OpenJournalofNeuroscience"EditorialBoardMember、
"JournalofExperimentalNeuroscience"HonoraryEditorialBoardMember、
"NeuroendocrinologyLetters"EditorialBoardMember、
"AnimalCellsandSystems"EditorialBoardMember、
"ZoologicalScience"EditorialBoardMember、
"FrontiersinIntegrativePharmacology"ReviewEditorialBoardMember、
日本生殖内分泌学会雑誌編集主幹、
比較内分泌学会Newsletter編集主幹、
日本比較生理生化学会誌編集委員等を務める。
国際比較内分泌学会連合評議員・国際会議プログラム委員、
アジア・オセアニア比較内分泌学会会長、
国際Cerebellum学会(SRC)学術顧問、
国際鳥類学会連合日本代表、
国際鳥類内分泌会議評議員・プログラム委員、
国際両生類爬虫類内分泌学・神経科学会議評議員、
国際神経ペプチド学会日本支部幹事、
日本比較内分泌学会会長、
日本動物学会理事、
日本生殖内分泌学会理事、
日本比較生理生化学会評議員、
日本ステロイドホルモン学会評議員、
日本下垂体研究会会長、
鳥類内分泌研究会代表世話人、
ニューロエソロジー談話会世話人、
生物脳科学研究会世話人等を務める。

受賞

Bargmann-Scharrer Award

2013年

第4回国際小脳学会シンポジウムMasao Ito Best Poster Award

2011年

Farner Medal: International Society for Avian Endocrinology

2008年

吉村賞: 日本下垂体研究会

2008年

日本比較内分泌学会第32回大会最優秀発表賞

2007年

日本下垂体研究会第22回学術集会最優秀発表賞

2007年

日本神経内分泌学会・日本下垂体研究会Brain-Pituitary 2005 優秀発表特別賞

2005年

日本神経内分泌学会・日本下垂体研究会Brain-Pituitary 2005 最優秀発表賞

2005年

Best Presentation Prize: British Society for Reproduction and Fertility

2003年

第27回日本比較内分泌学会 ベストポスター賞 2002

2002年

日本動物学会賞

2001年

第25回日本比較内分泌学会 ベストポスター賞

2000年

取材ガイド

カテゴリー
医歯薬学
専門分野
神経内分泌学、生殖内分泌学、脳科学
自己紹介コメント
重要な新規脳ホルモンの同定とそれらの生理機能、作用機構を解析している。この過程で、動物の生殖を抑制する新規脳ホルモンである生殖腺刺激ホルモン放出抑制ホルモン(GnIH)を発見した(Farner Medal, 2008)。また、動物の脳がステロイド(ニューロステロイド)を合成することを見いだした(動物学会賞, 2001)。さらに、動物の活動性を高める新規のニューロステロイドを発見した(Bargmann-Scharrer Award, 2013)。
キーワード
脳ホルモン、神経ステロイド、神経ペプチド

研究分野

キーワード

神経内分泌学、行動神経内分泌学、生殖内分泌学に関する総合脳科学

科研費分類

生物学 / 基礎生物学 / 形態・構造

論文

Review: 7α-Hydroxypregnenolone regulating locomotor behavior identified in the brain and pineal gland across vertebrates

K. Tsutsui, S. Haraguchi and H. Vaudry

Gen. Comp. Endocrinol.265p.97 - 1052018年09月-

DOI

Expression of steroidogenic enzymes and metabolism of steroids in COS-7 cells known as non-steroidogenic cells

Nozaki, Mitsuki; Haraguchi, Shogo; Haraguchi, Shogo; Miyazaki, Takuro; Shigeta, Daichi; Kano, Noriko; Lei, Xiao Feng; Kim-Kaneyama, Joo Ri; Minakata, Hiroyuki; Miyazaki, Akira; Tsutsui, Kazuyoshi

Scientific Reports8(1)2018年02月-2018年02月 

DOIScopus

詳細

概要:© 2018 The Author(s). The COS-7 (CV-1 in Origin with SV40 genes) cells are known as non-steroidogenic cells because they are derived from kidney cells and the kidney is defined as a non-steroidogenic organ. Therefore, COS-7 cells are used for transfection experiments to analyze the actions of functional molecules including steroids. However, a preliminary study suggested that COS-7 cells metabolize [ 3 H]testosterone to [ 3 H]androstenedione. These results suggest that COS-7 cells are able to metabolize steroids. Therefore, the present study investigated the expression of steroidogenic enzymes and the metabolism of steroids in COS-7 cells. RT-PCR analyses demonstrated the expressions of sev eral kinds of steroidogenic enzymes, such as cytochrome P450 side-chain cleavage enzyme, 3β-hydroxysteroid dehydrogenase/Δ 5 -Δ 4 isomerase, cytochrome P450 7α-hydroxylase, cytochrome P450 17α-hydroxylase/17,20-lyase, 17β-hydroxysteroid dehydrogenase, 5α-reductase, cytochrome P450 21-hydroxylase, cytochrome P450 11β-hydroxylase, and cytochrome P450 aromatase in COS-7 cells. In addition, steroidogenic enzymes 3β-HSD, P4507α, 5α-reductase, P450c17, P450c21, P450c11β, and 17β-HSD actively metabolized various steroids in cultured COS-7 cells. Finally, we demonstrated that 17β-HSD activity toward androstenedione formation was greater than other steroidogenic enzyme activities. Our results provide new evidence that COS-7 cells express a series of steroidogenic enzyme mRNAs and actively metabolize a variety of steroids.

Strain differences in intermale aggression and possible factors regulating increased aggression in Japanese quail

Maekawa, Fumihiko; Nagino, Koki; Nagino, Koki; Yang, Jiaxin; Htike, Nang T.T.; Tsukahara, Shinji; Tsukahara, Shinji; Ubuka, Takayoshi; Ubuka, Takayoshi; Tsutsui, Kazuyoshi; Kawashima, Takaharu

General and Comparative Endocrinology256p.63 - 702018年01月-2018年01月 

DOIScopus

詳細

ISSN:00166480

概要:© 2017 Elsevier Inc. The National Institute for Environmental Studies (NIES) of Japan established a strain of Japanese quail (Coturnix japonica) known as NIES-L by rotation breeding in a closed colony for over 35 years; accordingly, the strain has highly inbred-like characteristics. Another strain called NIES-Brn has been maintained by randomized breeding in a closed colony to produce outbred-like characteristics. The current study aimed to characterize intermale aggressive behaviors in both strains and to identify possible factors regulating higher aggression in the hypothalamus, such as sex hormone and neuropeptide expression. Both strains displayed a common set of intermale aggressive behaviors that included pecking, grabbing, mounting, and cloacal contact behavior, although NIES-Brn quail showed significantly more grabbing, mounting, and cloacal contact behavior than did NIES-L quail. We examined sex hormone levels in the blood and diencephalon in both strains. Testosterone concentrations were significantly higher in the blood and diencephalon of NIES-Brn quail compared to NIES-L quail. We next examined gene expression in the hypothalamus of both strains using an Agilent gene expression microarray and real-time RT-PCR and found that gene expression of mesotocin (an oxytocin homologue) was significantly higher in the hypothalamus of NIES-Brn quail compared to NIES-L quail. Immunohistochemistry of the hypothalamus revealed that numbers of large cells (cell area > 500 μm 2 ) expressing mesotocin were significantly higher in the NIES-Brn strain compared to the NIES-L strain. Taken together, our findings suggest that higher testosterone and mesotocin levels in the hypothalamus may be responsible for higher aggression in the NIES-Brn quail strain.

Discovery of GnIH and its role in hypothyroidism-Induced delayed puberty

Tsutsui, Kazuyoshi; Son, You Lee; Kiyohara, Mika; Miyata, Ichiro

Endocrinology159(1)p.62 - 682018年01月-2018年01月 

PubMedDOIScopus

詳細

ISSN:00137227

概要:Copyright © 2018 Endocrine Society. It is known that hypothyroidism delays puberty in mammals. Interaction between the hypothalamo-pituitary-thyroid (HPT) and hypothalamo-pituitary-gonadal (HPG) axes may be important processes in delayed puberty. Gonadotropin-inhibitory hormone (GnIH) is a newly discovered hypothalamic neuropeptide that inhibits gonadotropin synthesis and release in quail. It now appears that GnIH is conserved across various mammals and primates, including humans, and inhibits reproduction. We have further demonstrated that GnIH is involved in pubertal delay induced by thyroid dysfunction in female mice. Hypothyroidism delays pubertal onset with the increase in hypothalamic GnIH expression and the decrease in circulating gonadotropin and estradiol levels. Thyroid status regulates GnIH expression by epigenetic modification of the GnIH promoter region. Furthermore, knockout of GnIH gene abolishes the effect of hypothyroidism on delayed pubertal onset. Accordingly, it is considered that GnIH is a mediator of pubertal disorder induced by thyroid dysfunction. This is a novel function of GnIH that interacts between the HPT-HPG axes in pubertal onset delay. This mini-review summarizes the structure, expression, and function of GnIH and highlights the action of GnIH in pubertal disorder induced by thyroid dysfunction.

Editorial: The Roles of GnIH in reproductive function and behavior

Ubuka, Takayoshi; Parhar, Ishwar; Kriegsfeld, Lance J.; Tsutsui, Kazuyoshi

Frontiers in Endocrinology9(JAN)2018年01月-2018年01月 

DOIScopus

Gonadotropin-inhibitory hormone mediates behavioral stress responses

Ubuka, Takayoshi; Parhar, Ishwar S.; Tsutsui, Kazuyoshi

General and Comparative Endocrinology2018年01月-2018年01月 

DOIScopus

詳細

ISSN:00166480

概要:© 2018 Elsevier Inc. Gonadotropin-inhibitory hormone (GnIH) is an inhibitor of the hypothalamic-pituitary-gonadal (HPG) axis. GnIH is also called RFamide-related peptide (RFRP) as GnIH peptides have a characteristic C-terminal LPXRFiamide (X = L or Q) sequence. GnIH is thought to be the mediator of stress by negatively regulating the HPG axis as various stressors increase GnIH mRNA, GnIH peptide or GnIH neuronal activity. On the other hand, GnIH may also mediate behavioral stress responses as GnIH neuronal fibers and GnIH receptors are widely located in the limbic system of telencephalon, diencephalon and midbrain area. Previous studies have shown that intracerebroventricular (i.c.v.) administration of GnIH (RFRP) blocks morphine-induced analgesia in hot plate and formalin injection tests in rats suggesting that GnIH increases sensitivity to pain. GnIH (RFRP) also increases anxiety-like behavior in rats. RNA interference of GnIH gene (GnIH RNAi) increases locomotor activity of white-crowned sparrow and Japanese quail and i.c.v. administration of GnIH decreases GnIH RNAi induced locomotor activity. It was further shown that i.c.v. administration of GnIH (RFRP) decreases aggressive behavior in male quail and sexual behavior in male rats, female white-crowned sparrow and female hamsters. These results suggest that GnIH decreases threat to homeostasis of the organism by increasing pain sensitivity, anxiety and decreasing locomotor activity, aggressive behavior and sexual behavior. GnIH may also mediate the effect of stress on behavior.

Ontogeny of gonadotrophin-inhibitory hormone in the cichlid fish Cichlasoma dimerus.

M. P. Di Yorio, J. E. Sallemi, F. J. Toledo Solís, D. I. Pérez Sirkin, T. H. Delgadin, K. Tsutsui and P. G. Vissio

J. Neuroendocrinol.30::e126082018年-

DOI

Brain mapping of the gonadotropin-inhibitory hormone-related peptide 2 with a novel antibody suggests a connection with emotional reactivity in the Japanese quail (Coturnix japonica).

K. Poissenot, K. Anger, P. Constantin, F. Cornilleau, D. Lomet, K. Tsutsui, H. Dardente, L. Calandreau and M. Beltramo Massimiliano

J. Comp. Neurol.,in press2018年-

Action of neurotensin, corticotropin-releasing hormone, and RFamide-related peptide-3 in E2-induced negative feedback control: studies using a mouse arcuate nucleus hypothalamic cell model.

T. Tumurbaatar,, H. Kanasaki, A. Oride, T. Hara, H. Okada, K. Tsutsui and S. Kyo

Biol. Reprod.2018年-2018年

DOI

Morphological relationship between GnIH and GnRH neurons in the brain of the Neotropical cichlid fish Cichlasoma dimerus.

M. P. Di Yorio, D. I. Pérez Sirkin, J. A. Muñoz-Cueto3, T. H. Delgadin, K. Tsutsui, G. M. Somoza and P. G. Vissio

Gen. Comp. Endocrinol.in press2018年-2018年

Sex and age dependent variation of gonadal NO and RFRP-3 (a mammalian GnIH ortholog) in mouse, Mus musculus: A possible cause of alteration in mammalian sex steroids.

V. P. Singh, K. Tsutsui and C. M. Chaturvedi U

Gen. Comp. Endocrinol.in press2018年-2018年

Fast free of acrylamide clearing tissue (FACT) for clearing, immunolabeling and three-dimensional imaging of partridge tissues.

F. M. Rezazadeh, S. Saedi, F. Rahmanifar, M. R. Namavar, M. Dianatpour, N. Tanideh, A. Akhlaghi, A. Niazi, A. A. Monfared, K. Tsutsui, M. R.Shirazi and A. Tamadon

Microsc. Res. Tech.in press2018年-2018年

The Roles of RFamide-related peptides (RFRPs), mammalian gonadotropin-inhibitory hormone (GnIH) orthologues, in female reproduction.

H. Wang, A. Khoradmehr, M. Jalali, M. S. Salehi, K. Tsutsui, M. R. J. Shirazi, and A.Tamadon

J. Basic Med. Sci.in press2018年-2018年

Kobayashi Award: Discovery of cerebellar and pineal neurosteroids and their biological actions on the growth and survival of Purkinje cells during development (review)

K. Tsutsui

Gen. Comp. Endocrinol.p.in press2018年-

Revew: How to contribute to the progress of reproductive neuroendocrinology: Discovery of novel neuropeptides regulating reproductive physiology and behavior

K. Tsutsui

EC Endocrinol. Metab. Res.3p.205 - 2072018年-

Review: Comparative and evolutionary aspects of gonadotropin-inhibitory hormone and FMRFamide-like peptide systems

T. Ubuka and K. Tsutsui

Front. Neurosci.in press2018年-

Review: Brain-derived steroids, behavior and endocrine conflicts across life history stages in birds.

J. C. Wingfield, D. W. Wacker, G. E. Bentley and K. Tsutsui

Front. Endocrinol.in press2018年-

Review: Gonadotropin-inhibitory hormone (GnIH) and its mammalian ortholog RFamide-related peptide-3 (RFRP-3): Discovery and functional implications for reproduction and stress

L. J. Kriegsfeld, G. E. Bentley and K. Tsutsui

J. Neuroendocrinol.in press2018年-

Short-review: Brain and pineal 7α-hydroxypregnenolone regulating locomotor behavior: Discovery, progress and prospect

K. Tsutsui, S. Haraguchi and T. Ubuka

Neuropsychiatry8p.739 - 7442018年-

Review: Molecular mechanisms of the regulation of reproductive physiology and behavior by gonadotropin-inhibitory hormone (GnIH)

K. Tsutsui and T. Ubuka

Reprod. Med. Biol.in press2018年-

Review: How to Contribute to the Progress of Neuroendocrinology: Discovery of GnIH and Progress of GnIH Research

K. Tsutsui and T. Ubuka

Front. Endocrinol.in press2018年-

Editorial: The roles of GnIH in reproductive function and behavior

T. Ubuka, I. Parhar1, L. J. Kriegsfeld and K. Tsutsui

Front. Endocrinol.9(Article 19)2018年-

DOI

Mini-review: Neural versus gonadal GnIH: Are they independent systems?

G. E. Bentley, K. Wilsterman, D. K. Ernst, S. E. Lynn, M. J. Dickens, R. M. Calisi, L. J. Kriegsfeld, D. Kaufer, A. C. Geraghty, K. Kangas, N. L. McGuire and K. Tsutsui

J. Integrative Comp. Biol.57(6)p.1194 - 12032017年12月-

DOI

Involvement of gonadotropin-inhibitory hormone in pubertal disorders induced by thyroid status

Kiyohara, Mika; Son, You Lee; Tsutsui, Kazuyoshi

Scientific Reports7(1)2017年12月-2017年12月 

DOIScopus

詳細

概要:© 2017 The Author(s). Thyroid disorders cause abnormal puberty, indicating interactions between the hypothalamus-pituitary-thyroid (HPT) and hypothalamus-pituitary-gonadal (HPG) axes, which are important in pubertal development. The hypothalamic gonadotropin-inhibitory hormone (GnIH) was shown to be decreased in the early prepubertal stage, suggesting the role of GnIH on pubertal onset. Here, we investigated whether thyroid dysfunction affects pubertal onset in female mice via GnIH regulation. Hypothyroidism showed delayed pubertal onset with increased GnIH expression and reduced pituitary-gonadal activity. Remarkably, knockout of GnIH prevented the effect of hypothyroidism to delay the pubertal onset, resulting in indistinguishable pubertal timing in GnIH-knockout female mice between control and hypothyroidism-induced group, indicating that increased GnIH expression induced by hypothyroidism may lead to delayed puberty. In contrast, hyperthyroidism led to a decrease in GnIH expression, however pubertal onset was normal, implying further reduction of the inhibitory GnIH had little effect on the phenotypical change. Critically, thyroid hormone suppressed GnIH expression in hypothalamic explants and GnIH neurons expressed thyroid hormone receptors to convey the thyroid status. Moreover, the thyroid status highly regulated the chromatin modifications of GnIH promoter, H3acetylation and H3K9tri-methylation. These findings indicate a novel function of GnIH to mediate HPT-HPG interactions that contribute to proper pubertal development.

Direct effects of RFRP-1, a mammalian GnIH ortholog, on ovarian activities of the cyclic mouse

Dave, Anushree; Krishna, Amitabh; Tsutsui, Kazuyoshi

General and Comparative Endocrinology252p.193 - 1992017年10月-2017年10月 

PubMedDOIScopus

詳細

ISSN:00166480

概要:© 2017 Elsevier Inc. Arg(R)-Phe(F)-amide related peptide-1 (RFRP-1) and -3 (RFRP-3) are known as mammalian orthologs of gonadotropin-inhibitory hormone (GnIH). In mammals, these RFRPs are expressed not only in the hypothalamus and but also in gonads. Inhibitory roles of the hypothalamic and gonadal RFRP-3 in reproduction have been documented in mammals. However, functional roles of the hypothalamic and gonadal RFRP-1 in reproduction are still unclear in mammals. Therefore, in vitro studies were conducted to elucidate the direct effect of RFRP-1, a mammalian GnIH ortholog, on ovarian activities, such as steroidogenesis, apoptosis, cell proliferation and metabolism in the cyclic mouse. The ovaries collected from the proestrus mice were cultured in vitro with different doses (Control, 1 ng/ml, 10 ng/ml and 100 ng/ml) of RFRP-1 for 24 h at 37 °C. A significant dose-dependent increase in estradiol release from the ovary was detected after the treatment of RFRP-1. Therefore, changes in the ovarian activities, such as steroidogenic markers (luteinizing hormone receptors; LH-R and 3β-hydroxysteroid dehydrogenase; 3β-HSD), apoptotic markers [Poly(ADP-ribose) polymerase-1; PARP-1 and cysteine-aspartic protease; caspase-3], a cell proliferation marker (proliferating cell nuclear antigen; PCNA) and metabolic markers (GLUT-4; glucose uptake) were assessed by the treatment of RFRP-1 in the proestrus ovary. The densitometry analysis showed the treatment of RFRP-1 significantly increased the expressions of LH-R and 3β-HSD, steroidogenic markers. In contrast, the expressions of PCNA, a cell proliferation maker; PARP-1 and caspase-3, apoptotic markers were significantly decreased. Interestingly, RFRP-1 treatment further increases significantly glucose uptake and GLUT-4 receptor expression. These findings indicate that RFRP-1 possesses a stimulatory effect on ovarian steroidogenesis in the proestrus mouse. This is the first evidence showing the direct action of RFRP-1 on steroidogenesis in any vertebrate. In addition, RFRP-1 may also act directly on ovarian folliculogenesis as an inhibitory factor.

The Arg–Phe-amide peptide 26RFa/glutamine RF-amide peptide and its receptor: IUPHAR Review 24

Leprince, Jérôme; Bagnol, Didier; Bureau, Ronan; Fukusumi, Shoji; Granata, Riccarda; Hinuma, Shuji; Larhammar, Dan; Primeaux, Stefany; Sopkova-de Oliveiras Santos, Jana; Tsutsui, Kazuyoshi; Ukena, Kazuyoshi; Vaudry, Hubert

British Journal of Pharmacology174(20)p.3573 - 36072017年10月-2017年10月 

DOIScopus

詳細

ISSN:00071188

概要:© 2017 The British Pharmacological Society The RFamide neuropeptide 26RFa was first isolated from the brain of the European green frog on the basis of cross-reactivity with antibodies raised against bovine neuropeptide FF (NPFF). 26RFa and its N-terminally extended form glutamine RF-amide peptide (QRFP) have been identified as cognate ligands of the former orphan receptor GPR103, now renamed glutamine RF-amide peptide receptor (QRFP receptor). The 26RFa/QRFP precursor has been characterized in various mammalian and non-mammalian species. In the brain of mammals, including humans, 26RFa/QRFP mRNA is almost exclusively expressed in hypothalamic nuclei. The 26RFa/QRFP transcript is also present in various organs especially in endocrine glands. While humans express only one QRFP receptor, two isoforms are present in rodents. The QRFP receptor genes are widely expressed in the CNS and in peripheral tissues, notably in bone, heart, kidney, pancreas and testis. Structure–activity relationship studies have led to the identification of low MW peptidergic agonists and antagonists of QRFP receptor. Concurrently, several selective non-pept idic antagonists have been designed from high-throughput screening hit optimization. Consistent with the widespread distribution of QRFP receptor mRNA and 26RFa binding sites, 26RFa/QRFP exerts a large range of biological activities, notably in the control of energy homeostasis, bone formation and nociception that are mediated by QRFP receptor or NPFF2. The present report reviews the current knowledge concerning the 26RFa/QRFP-QRFP receptor system and discusses the potential use of selective QRFP receptor ligands for therapeutic applications.

Noradrenergic modulation of gonadotrophin-inhibitory hormone gene expression in the brain of Japanese quail

Tobari, Y.; Kansaku, N.; Tsutsui, K.

Journal of Neuroendocrinology29(8)2017年08月-2017年08月 

DOIScopus

詳細

ISSN:09538194

概要:© 2017 British Society for Neuroendocrinology Gonadotrophin-inhibitory hormone (GnIH) is a hypothalamic neuropeptide that inhibits gonadotrophin synthesis and release in birds and mammals. In Japanese quail, GnIH neurones express the noradrenergic receptor and receive noradrenergic innervation. Treatment with noradrenaline (NA) stimulates GnIH release from diencephalic tissue blocks in vitro. However, the effects of NA on hypothalamic GnIH gene expression have not been determined. We investigated noradrenergic regulation of GnIH gene expression in the brain of male quail using the selective noradrenergic neurotoxin N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine hydrochloride (DSP-4). We first showed that DSP-4 reduced the number of noradrenergic (dopamine-β-hydroxylase immunoreactive) cells in the locus coeruleus (LoC) and specifically lowered the NA concentration in the hypothalamus of male quail. Other monoamines, such as dopamine and serotonin, were not affected by drug treatment. DSP-4 did not decrease the numbers of noradrenergic cells of the lateral tegmental cell group, nor the plasma NA concentration. Decreased hypothalamic NA levels after DSP-4 treatment did not change GnIH gene expression in the brains of quail during their interaction with conspecifics. On the other hand, GnIH gene expression increased in the brains of quail socially isolated for 1 hour after DSP-4 treatment. These results suggest that some noradrenergic neurones have inhibitory effects on GnIH gene expression of the hypothalamus in solitary quail.

Review: Structure, Function and Evolution of GnIH

K. Tsutsui, T. Osugi, Y. L. Son and T. Ubuka

Gen. Comp. Endocrinol.264p.48 - 572017年07月-

DOI

Seasonal changes in hypothalamic gonadotropin inhibitory hormone expression in the paraventricular nucleus of chukar partridge (Alectoris chukar)

Rezazadeh, Farzad Mohammad; Shirazi, Mohammad Reza Jafarzadeh; Zamiri, Mohammad Javad; Salehi, Mohammad Saied; Namavar, Mohammad Reza; Akhlaghi, Amir; Tamadon, Amin; Tsutsui, Kazuyoshi

Animal Reproduction14(2)p.452 - 4582017年04月-2017年04月 

DOIScopus

詳細

ISSN:18069614

概要:Gonadotropin inhibitory hormone (GnIH) as a hypothalamic neuropeptide inhibits the synthesis and release of gonadotropins via affecting gonadotropin releasing hormone (GnRH) neurons and could be a key neuropeptide in regulating seasonal breeding in birds. The aim of the present study was to investigate the expression of GnIH in the hypothalamus of male and female chukar partridges (Alectoris chukar) during the breeding and non-breeding seasons. In breeding (May) and non-breeding (January) seasons, the brains of sexually-matured male (n = 10) and female (n = 10) chukar partridges were removed following fixation. Sections (30 μm) were prepared from the entire diencephalon and stained immunohistochemically. GnIH-immunoreactive neurons were primarily found in paraventricular nucleus, and few positive neurons were detected in dorsomedial nucleus. The numbers f GnIH-immunoreactive neurons were significantly lower in the breeding season compared with the non-breeding soeason in both male and female (P < 0.05). There were no significant differences in the number of GnIH neurons in paraventricular nucleus between the sexes. Gonadal weight and volume in male and female partridges were significantly higher in the breeding season. The results showed that GnIH neurons may partly contribute to the regulation of the seasonal breeding in the chukar partridge.

Gonadotropin-inhibitory hormone (GnIH) in the amphibian brain and its relationship with the gonadotropin releasing hormone (GnRH) system: An overview

Jadhao, Arun G.; Pinelli, Claudia; D'Aniello, Biagio; Tsutsui, Kazuyoshi

General and Comparative Endocrinology240p.69 - 762017年01月-2017年01月 

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ISSN:00166480

概要:© 2016 Elsevier Inc.It is well known that the hypothalamic neuropeptide gonadotropin-releasing hormone (GnRH) plays an important role as a primary factor regulating gonadotropin secretion in reproductive processes in vertebrates. The discovery of the presence of a gonadotropin-inhibitory hormone (GnIH) in the brains of birds has further contributed to our understanding of the reproduction control by the brain. GnIH plays a key role in inhibition of reproduction and acts on the pituitary gland and GnRH neurons via a novel G protein-coupled receptor (GPR147). GnIH decreases gonadotropin synthesis and release, thus inhibiting gonadal development and maintenance. The GnRH and GnIH neuronal peptidergic systems are well reported in mammals and birds, but limited information is available regarding their presence and localization in the brains of other vertebrate species, such as reptiles, amphibians and fishes. The aim of this review is to compile and update information on the localization of GnRH and GnIH neuronal systems, with a particular focus on amphibians, summarizing the neuroanatomical distribution of GnIH and GnRH and emphasizing the discovery of GnIH based on RFamide peptides and GnIH orthologous peptides found in other vertebrates and their functional significance.

日本比較内分泌学会小林賞を受賞して
新規脳ホルモンの発見と生理機能の解明:比較解析から普遍原理の理解

筒井 和義

比較内分泌学43(161)p.54 - 582017年-2017年

CiNii

詳細

ISSN:1882-6636

Endocrine disrupting pesticides impair the neuroendocrine regulation of reproductive behaviors an secondary sexual characters of red munia (Amandava amandava)

S. P. Pandey, K. Tsutsui and B. Mohanty

Physiol. Behav.173p.15 - 222017年-

Thyroid disrupting pesticides impair the hypothalamic-pituitary-testicular axis of a wildlife bird, Amandava amandava

B. Mohanty, S.P. Pandey, K. Tsutsui

Reprod. Toxicol.71p.32 - 412017年-

DOI

Sex differences in the photoperiodic regulation of RF-Amide related peptide (RFRP) and its receptor GPR147 in the syrian hamster

Henningsen, Jo B.; Poirel, Vincent Joseph; Mikkelsen, Jens D.; Tsutsui, Kazuyoshi; Simonneaux, Valérie; Gauer, François

Journal of Comparative Neurology524(9)p.1825 - 18382016年06月-2016年06月 

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ISSN:00219967

概要:© 2015 Wiley Periodicals, Inc.RF-(Arg-Phe) related peptides (RFRP-1 and -3) are considered to play a role in the seasonal regulation of reproduction; however, the effect of the peptides depends on species and gender. This study aimed at comparing the RFRP system in male and female Syrian hamsters over long and short photoperiods to investigate the neuroanatomical basis of these differential effects. The neuroanatomical distribution of RFRP neurons and fibers, revealed using an antiserum recognizing RFRP-1 and -3, as well as GPR147 mRNA, are similar in male and female Syrian hamsters. RFRP neurons are mainly found in the medial hypothalamus, whereas RFRP projections and GPR147 mRNA are observed in the preoptic area, anteroventral-periventricular nucleus, suprachiasmatic nucleus, paraventricular nucleus, bed nucleus of the stria terminalis, ventromedial hypothalamus, habenular nucleus, and arcuate nucleus. The number of RFRP neurons is higher in females than in males, and in both sexes, the number of RFRP neurons is reduced in short photoperiods. GPR147 mRNA levels are higher in females than in males and are downregulated in short photoperiods, particularly in females. Interestingly, the number of RFRP-positive fibers in the anteroventral-periventricular nucleus is higher only in females adjusted to a short photoperiod. Our results suggest that the RFRP system, which is strongly regulated by photoperiod in both male and female Syrian hamsters, is particularly important in females, with a distinct role in the anteroventral-periventricular nucleus, possibly in the regulation of the preovulatory luteinizing hormone surge via kisspeptin neurons. J. Comp. Neurol. 524:1825-1838, 2016.

Inhibitory action of gonadotropin-inhibitory hormone on the signaling pathways induced by kisspeptin and vasoactive intestinal polypeptide in GnRH neuronal cell line, GT1-7

Son, You Lee; Ubuka, Takayoshi; Soga, Tomoko; Yamamoto, Kazutoshi; Bentley, George E.; Tsutsui, Kazuyoshi

FASEB Journal30(6)p.2198 - 22102016年06月-2016年06月 

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詳細

ISSN:08926638

概要:© FASEB.Gonadotropin-inhibitory hormone (GnIH) acts as a negative regulator of reproduction by acting on gonadotropes and gonadotropin-releasing hormone (GnRH) neurons. Despite its functional significance, the molecular mechanism of GnIH action in the target cells has not been fully elucidated. To expand our previous study on GnIH actions in gonadotropes, we investigated the potential signal transduction pathway that conveys the inhibitory action of GnIH in GnRH neurons by using the GnRH neuronal cell line, GT1-7. We examined whether GnIH inhibits the action of kisspeptin and vasoactive intestinal polypeptide (VIP), positive regulators of GnRH neurons. Although GnIH significantly suppressed the stimulatory effect of kisspeptin on GnRH release in hypothalamic culture, GnIH had no inhibitory effect on kisspeptin stimulation of serum response element and nuclear factor of activated T-cell response element activities and ERK phosphorylation, indicating that GnIH may not directly inhibit kisspeptin signaling in GnRH neurons. On the contrary, GnIH effectively eliminated the stimulatory effect of VIP on p38 and ERK phosphorylation, c-Fos mRNA expression, and GnRH release. The use of pharmacological modulators strongly demonstrated the specific inhibitory action of GnIH on the adenylate cyclase/cAMP/protein kinase A pathway, suggesting a common inhibitory mechanism of GnIH action in GnRH neurons and gonadotropes.

Avian test battery for the evaluation of developmental abnormalities of neuro- and reproductive systems

Kawashima, Takaharu; Ahmed, Walaa M S; Ahmed, Walaa M S; Nagino, Koki; Nagino, Koki; Ubuka, Takayoshi; Tsutsui, Kazuyoshi

Frontiers in Neuroscience10(JUN)2016年06月-2016年06月 

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詳細

ISSN:16624548

概要:© 2016 Kawashima, Ahmed, Nagino, Ubuka and Tsutsui.Most of the currently used toxicity assays for environmental chemicals use acute or chronic systemic or reproductive toxicity endpoints rather than neurobehavioral endpoints. In addition, the current standard approaches to assess reproductive toxicity are time-consuming. Therefore, with increasing numbers of chemicals being developed with potentially harmful neurobehavioral effects in higher vertebrates, including humans, more efficient means of assessing neuro- and reproductive toxicity are required. Here we discuss the use of a Galliformes-based avian test battery in which developmental toxicity is assessed by means of a combination of chemical exposure during early embryonic development using an embryo culture system followed by analyses after hatching of sociosexual behaviors such as aggression and mating and of visual memory via filial imprinting. This Galliformes-based avian test battery shows promise as a sophisticated means not only of assessing chemical toxicity in avian species but also of assessing the risks posed to higher vertebrates, including humans, which are markedly sensitive to nervous or neuroendocrine system dysfunction.

The ecological and physiological bases of variation in the phenology of gonad growth in an urban and desert songbird

Davies, Scott; Lane, Samuel; Meddle, Simone L.; Tsutsui, Kazuyoshi; Deviche, Pierre

General and Comparative Endocrinology230-231p.17 - 252016年05月-2016年05月 

DOIScopus

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ISSN:00166480

概要:© 2016 The Authors.Birds often adjust to urban areas by advancing the timing (phenology) of vernal gonad growth. However, the ecological and physiological bases of this adjustment are unclear. We tested whether the habitat-related disparity in gonad growth phenology of male Abert's towhees, Melozone aberti, is due to greater food availability in urban areas of Phoenix, Arizona USA or, alternatively, a habitat-related difference in the phenology of key food types. To better understand the physiological mechanism underlying variation in gonad growth phenology, we compared the activity of the reproductive system at all levels of hypothalamo-pituitary-gonadal (HPG) axis. We found no habitat-associated difference in food availability (ground arthropod biomass), but, in contrast to the seasonal growth of leaves on desert trees, the leaf foliage of urban trees was already developed at the beginning of our study. Multiple estimates of energetic status did not significantly differ between the non-urban and urban towhees during three years that differed in the habitat-related disparity in gonad growth and winter precipitation levels. Thus, our results provide no support for the hypothesis that greater food abundance in urban areas of Phoenix drives the habitat-related disparity in gonad growth phenology in Abert's towhees. By contrast, they suggest that differences in the predictability and magnitude of change in food availability between urban and desert areas of Phoenix contribute to the observed habitat-related disparity in gonad growth. Endocrine responsiveness of the gonads may contribute to this phenomenon as desert - but not urban - towhees had a marked plasma testosterone response to GnRH challenge.

Apoptosis-mediated testicular alteration in Japanese quail (Coturnix coturnix japonica) in response to temporal phase relation of serotonergic and dopaminergic oscillations

Banerjee, Somanshu; Tsutsui, Kazuyoshi; Chaturvedi, Chandra Mohini

Journal of Experimental Biology219(10)p.1476 - 14872016年05月-2016年05月 

DOIScopus

詳細

ISSN:00220949

概要:© 2016. Published by The Company of Biologists Ltd.Reproductive performance of many avian species, including Japanese quail, is reported to be modulated by specific temporal phase relation of serotonergic and dopaminergic oscillations. Accordingly, it has been shown that the serotonin precursor 5-HTP and the dopamine precursor L-DOPA given 8 h apart induce gonadal suppression and given 12 h apart lead to gonadal stimulation, while other temporal relationships were found to be ineffective. In the present study, we investigated the effects of 8- and 12-h phase relation of neural oscillations on testicular responses including expression of GnRH-I, GnIH, pro-apoptotic proteins (p53 and Bax), inactive and active executioner caspase-3, and the uncleaved DNA repair enzyme PARP-1. Testicular volume and mass decreased significantly in 8-h quail and increased in 12-h quail compared with controls. Expression of ir-GnIH, p53, Bax and active-caspase-3 increased and that of GnRH-I, pro-caspase-3 and uncleaved PARP-1 decreased in 8-h quail compared with controls. A TUNEL assay also confirmed testicular regression in these quail. Testes of 12-h quail exhibited significantly increased expression of GnRH-I, pro-caspase- 3 and uncleaved PARP-1 compared with the control group. Our findings suggest that differential response of avian testes to 8- and 12-h phase relation of serotonergic and dopaminergic neural oscillations may be attributed to autocrine/paracrine action of GnIH expression, which is upregulated in regressed testes, leading to apoptotic changes, and downregulated in developed testes, causing apoptotic inhibition. It is concluded that specific phase relation of neural oscillations may modulate the local testicular GnRH-GnIH system and alter the apoptotic mechanism in quail testes. Moreover, these findings highlight the physiological effects of time-dependent drug delivery, including the specific time intervals between two drugs.

Gonadotrophin-Inhibitory Hormone in the Cichlid Fish Cichlasoma dimerus: Structure, Brain Distribution and Differential Effects on the Secretion of Gonadotrophins and Growth Hormone

Di Yorio, M. P.; Pérez Sirkin, D. I.; Delgadin, T. H.; Shimizu, A.; Tsutsui, K.; Somoza, G. M.; Vissio, P. G.

Journal of Neuroendocrinology28(5)2016年05月-2016年05月 

DOIScopus

詳細

ISSN:09538194

概要:© 2016 British Society for NeuroendocrinologyThe role of gonadotrophin-inhibitory hormone (GnIH) in the inhibition of the reproductive axis has been well-established in birds and mammals. However, its role in other vertebrates, such as the teleost fish, remains controversial. In this context, the present study aimed to evaluate whether GnIH modulates the release of gonadotrophins and growth hormone (GH) in the cichlid fish Cichlasoma dimerus. First, we partially sequenced the precursor polypeptide for GnIH and identified three putative GnIH peptides. Next, we analysed the expression of this precursor polypeptide via a polymerase chain reaction in the reproductive axis of both sexes. We found a high expression of the polypeptide in the hypothalamus and gonads of males. Immunocytochemistry allowed the observation of GnIH-immunoreactive somata in the nucleus posterioris periventricularis and the nucleus olfacto-retinalis, with no differences between the sexes. GnIH-immunoreactive fibres were present in all brain regions, with a high density in the nucleus lateralis tuberis and at both sides of the third ventricle. Finally, we performed in vitro studies on intact pituitary cultures to evaluate the effect of two doses (10−6 m and 10−8 m) of synthetic C. dimerus (cd-) LPQRFa-1 and LPQRFa-2 on the release of gonadotrophins and GH. We observed that cd-LPQRFa-1 decreased β-luteinising hormone (LH) and β-follicle-stimulating hormone (FSH) and also increased GH release to the culture medium. The release of β-FSH was increased only when it was stimulated with the higher cd-LPQRFa-2 dose. The results of the present study indicate that cd-LPQRFa-1, the cichlid fish GnIH, inhibits β-LH and β-FSH release and stimulates GH release in intact pituitary cultures of C. dimerus. The results also show that cd-LPQRF-2 could act as an β-FSH-releasing factor in this fish species.

Nucleotide sequence and expression of relaxin-like gonad-stimulating peptide gene in starfish Asterina pectinifera

Haraguchi, Shogo; Ikeda, Narumi; Abe, Michiko; Tsutsui, Kazuyoshi; Mita, Masatoshi

General and Comparative Endocrinology227p.115 - 1192016年02月-2016年02月 

DOIScopus

詳細

ISSN:00166480

概要:© 2015 Elsevier Inc.Starfish gonad-stimulating substance (GSS) is the only known invertebrate peptide hormone responsible for final gamete maturation, rendering it functionally analogous to gonadotropins in vertebrates. Because GSS belongs to the relaxin-like peptide family, we propose renaming for starfish gonadotropic hormone as relaxin-like gonad-stimulating peptide (RGP). This study examined the primary structure and expression regulation of the RGP gene in starfish Asterina pectinifera. RGP consisted of 3896 base pairs (bp) divided over two exons, exon 1 of 208 bp and exon 2 of 2277 bp, and one intron of 1411 bp. Promoter sequences, CAAT and TATA boxes, were present in the 5'-upstream region of the coding DNA sequence of RGP. The transcript was 2485 bases (b) in length. The AAUAAA polyadenylation signal was found in 3'-untranslated region over 2 kb away from the stop codon. This showed that only 14% of the RGP mRNA was translated into the peptide, because a size of the open-reading frame was 351 b. Furthermore, an analysis by using real-time quantitative PCR with specific primers for RGP showed that mRNA of RGP was expressed at high levels in the radial nerves. Expression was also observed in the cardiac stomachs, although the level was low, and trace levels were detected in the gonads, pyloric caeca and tube feet. This result suggests that the RGP gene is transcribed mainly in the radial nerves of A. pectinifera.

Molecular, cellular, morphological, physiological and behavioral aspects of gonadotropin-inhibitory hormone

Ubuka, Takayoshi; Son, You Lee; Tsutsui, Kazuyoshi

General and Comparative Endocrinology227p.27 - 502016年02月-2016年02月 

DOIScopus

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ISSN:00166480

概要:© 2015 Elsevier Inc.Gonadotropin-inhibitory hormone (GnIH) is a hypothalamic neuropeptide that was isolated from the brains of Japanese quail in 2000, which inhibited luteinizing hormone release from the anterior pituitary gland. Here, we summarize the following fifteen years of researches that investigated on the mechanism of GnIH actions at molecular, cellular, morphological, physiological, and behavioral levels. The unique molecular structure of GnIH peptide is in its LPXRFamide (X = L or Q) motif at its C-terminal. The primary receptor for GnIH is GPR147. The cell signaling pathway triggered by GnIH is initiated by inhibiting adenylate cyclase and decreasing cAMP production in the target cell. GnIH neurons regulate not only gonadotropin synthesis and release in the pituitary, but also regulate various neurons in the brain, such as GnRH1, GnRH2, dopamine, POMC, NPY, orexin, MCH, CRH, oxytocin, and kisspeptin neurons. GnIH and GPR147 are also expressed in gonads and they may regulate steroidogenesis and germ cell maturation in an autocrine/paracrine manner. GnIH regulates reproductive development and activity. In female mammals, GnIH may regulate estrous or menstrual cycle. GnIH is also involved in the regulation of seasonal reproduction, but GnIH may finely tune reproductive activities in the breeding seasons. It is involved in stress responses not only in the brain but also in gonads. GnIH may inhibit male socio-sexual behavior by stimulating the activity of cytochrome P450 aromatase in the brain and stimulates feeding behavior by modulating the activities of hypothalamic and central amygdala neurons.

RFamide peptides in agnathans and basal chordates

Osugi, Tomohiro; Son, You Lee; Ubuka, Takayoshi; Satake, Honoo; Tsutsui, Kazuyoshi

General and Comparative Endocrinology227p.94 - 1002016年02月-2016年02月 

DOIScopus

詳細

ISSN:00166480

概要:© 2015 Elsevier Inc.Since a peptide with a C-terminal Arg-Phe-NH2 (RFamide peptide) was first identified in the ganglia of the venus clam in 1977, RFamide peptides have been found in the nervous system of both invertebrates and vertebrates. In vertebrates, the RFamide peptide family includes gonadotropin-inhibitory hormone (GnIH), neuropeptide FF (NPFF), prolactin-releasing peptide (PrRP), pyroglutamylated RFamide peptide/26RFamide peptide (QRFP/26RFa), and kisspeptins (kiss1 and kiss2). They are involved in important functions such as the release of hormones, regulation of sexual or social behavior, pain transmission, reproduction, and feeding. In contrast to tetrapods and jawed fish, the information available on RFamide peptides in agnathans and basal chordates is limited, thus preventing further insights into the evolution of RFamide peptides in vertebrates. In this review, we focus on the previous research and recent advances in the studies on RFamide peptides in agnathans and basal chordates. In agnathans, the genes encoding GnIH, NPFF, and PrRP precursors and the mature peptides have been identified in lamprey (Petromyzon marinus) and hagfish (Paramyxine atami). Putative kiss1 and kiss2 genes have also been found in the genome database of lamprey. In basal chordates, namely, in amphioxus (Branchiostoma japonicum), a common ancestral form of GnIH and NPFF genes and their mature peptides, as well as the ortholog of the QRFP gene have been identified. The studies revealed that the number of orthologs of vertebrate RFamide peptides present in agnathans and basal chordates is greater than expected, suggesting that the vertebrate RFamide peptides might have emerged and expanded at an early stage of chordate evolution.

7α-Hydroxypregnenolone regulates diurnal changes in sexual behavior of male quail

Ogura, Yuki; Haraguchi, Shogo; Nagino, Koki; Ishikawa, Kei; Fukahori, Yoko; Tsutsui, Kazuyoshi

General and Comparative Endocrinology227p.130 - 1352016年02月-2016年02月 

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ISSN:00166480

概要:© 2015 Elsevier Inc.In the Japanese quail, 7α-hydroxypregnenolone, a previously undescribed avian neurosteroid, is actively produced in the brain. 7α-Hydroxypregnenolone acts as a novel neuronal activator to stimulate locomotor activity of quail. Therefore, in this study, we determined whether 7α-hydroxypregnenolone changes the expression of sexual behavior in Japanese quail. We first measured diurnal changes in sexual behavior of male quail exposed to a long-day photoperiod. We found that sexual behavior of male quail was high in the morning when endogenous 7α-hydroxypregnenolone level is high. Subsequently, we centrally administered 7α-hydroxypregnenolone in the evening when endogenous 7α-hydroxypregnenolone level is low. In the 30 min after intracerebroventricular (ICV) injection, 7α-hydroxypregnenolone dose dependently increased the frequency of sexual behavior of male quail. However, 7β-hydroxypregnenolone, a stereoisomer of 7α-hydroxypregnenolone, did not effect on the frequency of sexual behavior of male quail. In addition, to confirm the action of 7α-hydroxypregnenolone on sexual behavior, male birds received an ICV injection of ketoconazole, an inhibitor of cytochrome P450s, and behavioral experiments were performed in the morning. Ketoconazole significantly decreased the frequency of sexual behavior of male quail, whereas administration of 7α-hydroxypregnenolone to ketoconazole-treated males increased the frequency of their sexual behavior. These results indicate that 7α-hydroxypregnenolone regulates diurnal changes in sexual behavior of male quail.

Putting the brakes on reproduction: Implications for conservation, global climate change and biomedicine

Wingfield, John C.; Perfito, Nicole; Calisi, Rebecca; Bentley, George; Ubuka, T.; Mukai, M.; O'Brien, Sara; Tsutsui, K.

General and Comparative Endocrinology227p.16 - 262016年02月-2016年02月 

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ISSN:00166480

概要:© 2015 Elsevier Inc.Seasonal breeding is widespread in vertebrates and involves sequential development of the gonads, onset of breeding activities (e.g. cycling in females) and then termination resulting in regression of the reproductive system. Whereas males generally show complete spermatogenesis prior to and after onset of breeding, females of many vertebrate species show only partial ovarian development and may delay onset of cycling (e.g. estrous), yolk deposition or germinal vesicle breakdown until conditions conducive for ovulation and onset of breeding are favorable. Regulation of this "brake" on the onset of breeding remains relatively unknown, but could have profound implications for conservation efforts and for "mismatches" of breeding in relation to global climate change. Using avian models it is proposed that a brain peptide, gonadotropin-inhibitory hormone (GnIH), may be the brake to prevent onset of breeding in females. Evidence to date suggests that although GnIH may be involved in the regulation of gonadal development and regression, it plays more regulatory roles in the process of final ovarian development leading to ovulation, transitions from sexual to parental behavior and suppression of reproductive function by environmental stress. Accumulating experimental evidence strongly suggests that GnIH inhibits actions of gonadotropin-releasing hormones on behavior (central effects), gonadotropin secretion (central and hypophysiotropic effects), and has direct actions in the gonad to inhibit steroidogenesis. Thus, actual onset of breeding activities leading to ovulation may involve environmental cues releasing an inhibition (brake) on the hypothalamo-pituitary-gonad axis.

Oct-GnRH, the first protostomian gonadotropin-releasing hormone-like peptide and a critical mini-review of the presence of vertebrate sex steroids in molluscs

Minakata, Hiroyuki; Tsutsui, Kazuyoshi

General and Comparative Endocrinology227p.109 - 1142016年02月-2016年02月 

DOIScopus

詳細

ISSN:00166480

概要:© 2015 Elsevier Inc.In protostome and deuterosome invertebrates, neurosecretory cells play major roles in the endocrine system. The optic glands of cephalopods are indicators of sexual maturation. In mature octopuses, optic glands enlarge and secrete a gonadotropic hormone. A peptide with structural features similar to that of vertebrate gonadotropin-releasing hormone (GnRH) was isolated from the octopus, Octopus vulgaris, and was named oct-GnRH. The discovery of oct-GnRH has triggered structural determinations and predictions of other mollusc GnRH-like peptides in biochemical and in silico studies. Interestingly, cephalopods studied so far are characterized by a single molecular form of oct-GnRH with a C-terminal -Pro-Gly-NH2 sequence, which is critical for gonadotropin-releasing activity in vertebrates. Other molluscan GnRH-like peptides lack the C-terminal -Pro-Gly-NH2 sequence but have -X-NH2 or -Pro-Gly although all protostome GnRH-like peptides have yet to be sequenced. In marine molluscs, relationships between GnRH-like peptides and sex steroids have been studied to verify the hypothesis that molluscs have vertebrate-type sex steroid system. However, it is currently questionable whether such sex steroids are present and whether they play endogenous roles in the reproductive system of molluscs. Because molluscs uptake and store steroids from the environment and fishes release sex steroids into the external environment, it is impossible to rule out the contamination of vertebrate sex steroids in molluscs. The function of key enzymes of steroidogenesis within molluscs remains unclear. Thus, evidence to deny the existence of the vertebrate-type sex steroid system in molluscs has been accumulated. The elucidation of substances, which regulate the maturation and maintenance of gonads and other reproductive functions in molluscs will require rigorous and progressive scientific study.

Identification and localization of gonadotropin-inhibitory hormone (GnIH) orthologs in the hypothalamus of the red-eared slider turtle, Trachemys scripta elegans.

Ukena Kazuyoshi;Iwakoshi-Ukena Eiko;Osugi Tomohiro;Tsutsui Kazuyoshi

General and comparative endocrinology227p.69 - 762016年02月-2016年02月 

PubMedDOI

詳細

ISSN:1095-6840

概要::Gonadotropin-inhibitory hormone (GnIH) was discovered in 2000 as a novel hypothalamic neuropeptide that inhibited gonadotropin release in the Japanese quail. GnIH and its orthologs have a common C-terminal LPXRFamide (X=L or Q) motif, and have been identified in vertebrates from agnathans to humans, apart from reptiles. In the present study, we characterized a cDNA encoding GnIH orthologs in the brain of the red-eared slider turtle. The deduced precursor protein consisted of 205 amino-acid residues, encoding three putative peptide sequences that included the LPXRFamide motif at their C-termini. In addition, the precursor sequence was most similar to those of avian species. Immunoaffinity purification combined with mass spectrometry confirmed that three mature peptides were produced in the brain. In situ hybridization and immunohistochemistry showed that turtle GnIH-containing cells were restricted to the periventricular hypothalamic nucleus. Immunoreactive fibers were densely distributed in the median eminence. Thus, GnIH and related peptides may act on the pituitary to regulate pituitary hormone release in turtles as well as other vertebrates.

How to contribute to the progress of neuroendocrinology: New insights from discovering novel neuropeptides and neurosteroids regulating pituitary and brain functions.

Tsutsui Kazuyoshi

General and comparative endocrinology227p.3 - 1522016年02月-2016年02月 

PubMedDOI

詳細

ISSN:1095-6840

概要::Obtaining new insights by discovering novel neuropeptides and neurosteroids regulating pituitary and brain functions is essential for the progress of neuroendocrinology. At the beginning of 1970s, gonadotropin-releasing hormone (GnRH) was discovered in mammals. Since then, it was generally accepted that GnRH is the only hypothalamic neuropeptide regulating gonadotropin release in vertebrates. In 2000, however, gonadotropin-inhibitory hormone (GnIH), a novel hypothalamic neuropeptide that actively inhibits gonadotropin release, was discovered in quail. The follow-up studies demonstrated that GnIH acts as a new key player for regulation of reproduction across vertebrates. It now appears that GnIH acts on the pituitary and the brain to serve a number of behavioral and physiological functions. On the other hand, a new concept has been established that the brain synthesizes steroids, called neurosteroids. The formation of neurosteroids in the brain was originally demonstrated in mammals and subsequently in other vertebrates. Recently, 7α-hydroxypregnenolone was discovered as a novel bioactive neurosteroid inducing locomotor behavior of vertebrates, indicating that neurosteroidogenesis in the brain is still incompletely elucidated in vertebrates. At the beginning of 2010s, it was further found that the pineal gland actively produces neurosteroids. Pineal neurosteroids act on the brain to regulate locomotor rhythms and neuronal survival. Furthermore, the interaction of neuropeptides and neurosteroids is becoming clear. GnIH decreases aggressive behavior by regulating neuroestrogen synthesis in the brain. This review summarizes these new insights by discovering novel neuropeptides and neurosteroids in the field of neuroendocrinology.

Possible role of GnIH as a mediator between adiposity and impaired testicular function

Anjum, Shabana; Krishna, Amitabh; Tsutsui, Kazuyoshi

Frontiers in Endocrinology7(FEB)2016年01月-2016年01月 

DOIScopus

詳細

概要:© 2016 Anjum, Krishna and Tsutsui.The aim of the present study was to evaluate the roles of gonadotropin-inhibitory hormone (GnIH) as an endocrine link between increasing adiposity and impaired testicular function in mice. To achieve this, the effect of GnIH on changes in nutrients uptake and hormonal synthesis/action in the adipose tissue and testis was investigated simultaneously by in vivo study and separately by in vitro study. Mice were treated in vivo with different doses of GnIH for 8 days. In the in vitro study, adipose tissue and testes of mice were cultured with different doses of GnIH with or without insulin or LH for 24 h at 37°C. The GnIH treatment in vivo showed increased food intake, upregulation of glucose transporter 4 (GLUT4), and increased uptake of triglycerides (TGs) in the adipose tissue. These changes may be responsible for increased accumulation of fat in white adipose tissue, resulting in increase in the body mass. Contrary to the adipose tissue, treatment with GnIH both in vivo and in vitro showed decreased uptake of glucose by downregulation of glucose transporter 8 (GLUT8) expressions in the testis, which in turn resulted in the decreased synthesis of testosterone. The GnIH treatment in vivo also showed the decreased expression of insulin receptor protein in the testis, which may also be responsible for the decreased testicular activity in the mice. These findings thus suggest that GnIH increases the uptake of glucose and TGs in the adipose tissue, resulting in increased accumulation of fat, whereas simultaneously in the testis, GnIH suppressed the GLUT8-mediated glucose uptake, which in turn may be responsible for decreased testosterone synthesis. This study thus demonstrates GnIH as mediator of increasing adiposity and impaired testicular function in mice.

Neuropeptide Control of Feeding Behavior in Birds and Its Difference with Mammals

Tachibana, Tetsuya;Tsutsui, Kazuyoshi

FRONTIERS IN NEUROSCIENCE102016年-2016年

DOIWoS

詳細

ISSN:1662-453X

GnIH Control of Feeding and Reproductive Behaviors

Tsutsui, Kazuyoshi;Ubuka, Takayoshi

FRONTIERS IN ENDOCRINOLOGY72016年-2016年

DOIWoS

詳細

ISSN:1664-2392

Nucleotide sequence and expression of relaxin-like gonad-stimulating peptide gene in starfish Asterina pectinifera.

Haraguchi Shogo;Ikeda Narumi;Abe Michiko;Tsutsui Kazuyoshi;Mita Masatoshi

General and comparative endocrinology2272016年-2016年

PubMedDOI

詳細

ISSN:1095-6840

概要::Starfish gonad-stimulating substance (GSS) is the only known invertebrate peptide hormone responsible for final gamete maturation, rendering it functionally analogous to gonadotropins in vertebrates. Because GSS belongs to the relaxin-like peptide family, we propose renaming for starfish gonadotropic hormone as relaxin-like gonad-stimulating peptide (RGP). This study examined the primary structure and expression regulation of the RGP gene in starfish Asterina pectinifera. RGP consisted of 3896 base pairs (bp) divided over two exons, exon 1 of 208 bp and exon 2 of 2277 bp, and one intron of 1411 bp. Promoter sequences, CAAT and TATA boxes, were present in the 5'-upstream region of the coding DNA sequence of RGP. The transcript was 2485 bases (b) in length. The AAUAAA polyadenylation signal was found in 3'-untranslated region over 2kb away from the stop codon. This showed that only 14% of the RGP mRNA was translated into the peptide, because a size of the open-reading frame was 351 b. Furthermore, an analysis by using real-time quantitative PCR with specific primers for RGP showed that mRNA of RGP was expressed at high levels in the radial nerves. Expression was also observed in the cardiac stomachs, although the level was low, and trace levels were detected in the gonads, pyloric caeca and tube feet. This result suggests that the RGP gene is transcribed mainly in the radial nerves of A. pectinifera.

Food availability, energetic constraints and reproductive development in a wild seasonally breeding songbird

S. Davies, T. Cros, D. Richard, S. L. Meddle, K. Tsutsui and P. Deviche

Funct. Ecol.11p.1421 - 14342016年-

Nucleotide sequence and expression of relaxin-like gonad-stimulating peptide gene in starfish Asterine pectinifera.

M. Mita, S. Haraguchi, N. Ikeda, M. Abe and K. Tsutsui

Gen. Comp. Endocrinol.11p.1421 - 14342016年-

Possible hormonal interaction for eliciting courtship behavior in the male newt, Cynops pyrrhogaster

Toyoda, Fumiyo; Hasunuma, Itaru; Nakada, Tomoaki; Haraguchi, Shogo; Tsutsui, Kazuyoshi; Kikuyama, Sakae; Kikuyama, Sakae

General and Comparative Endocrinology224p.96 - 1032015年12月-2015年12月 

PubMedDOIScopus

詳細

ISSN:00166480

概要:© 2015 Elsevier Inc.Reproductive behavior in amphibians, as in other vertebrate animals, is under the control of multiple hormonal substances. Prolactin (PRL), arginine vasotocin (AVT), androgen, and 7α-hydroxypregnenolone (7α-OH PREG), four such substances with hormonal activity, are known to be involved in the expression of the tail vibration behavior which is the initial step of courtship performed by the male newt, Cynops pyrrhogaster. As current information on the interaction(s) between these hormones in terms of eliciting tail vibration behavior is limited, we have investigated whether the decline of expression of tail vibration behavior due to suppression of the activity of any one of these hormones can be restored by supplying any one of the other three hormones exogenously. Expression of the behavior was determined in terms of incidence (% of test animals exhibiting the behavior) and frequency (number of times that the behavior was repeated during the test period). Neither PRL nor androgen restored the decline in the incidence and frequency of the tail vibration behavior caused by the suppression of the activity of any one of other three hormones. AVT completely restored both the anti-PRL antibody-induced and flutamide (an androgen receptor antagonist)-induced, but not ketoconazole (an inhibitor of the steroidogenic CYP enzymes)-induced decline in the incidence and frequency of the tail vibration behavior. The neurosteroid, 7α-OH PREG, failed to restore flutamide-induced decline in the incidence and frequency of the behavior. However, it was able to restore both anti-PRL antibody-induced and AVT receptor antagonist-induced decline in the incidence, but not in the frequency of the behavior. In another experiment designed to see the activity of hormones enhancing the frequency of the tail vibration behavior, AVT was revealed to be more potent than 7α-OH PREG. The role of each hormonal substance in determining the expression of the tail vibration behavior was discussed based on the results.

A new relaxin-like gonad-stimulating peptide identified in the starfish Asterias amurensis

Mita, Masatoshi; Daiya, Misaki; Haraguchi, Shogo; Haraguchi, Shogo; Tsutsui, Kazuyoshi; Nagahama, Yoshitaka

General and Comparative Endocrinology222p.144 - 1492015年10月-2015年10月 

DOIScopus

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ISSN:00166480

概要:© 2015 Elsevier Inc. Relaxin-like gonad-stimulating peptide (RGP) of starfish Asterina pectinifera was the first invertebrate gonadotropin to have its chemical structure identified. However, it is unclear whether gonadotropic hormones in other species starfish are relaxin-like peptides. Thus, this study tried to identify the molecular structure of gonadotropic hormone in Asterias amurensis. As a result, we identified A. amurensis gonadotropic hormone as the RGP (AamRGP). The DNA sequence encoding AamRGP consisted of 330 base pairs with an open reading frame encoding a peptide of 109 amino acids (aa), including a signal peptide (26 aa), B-chain (20 aa), C-peptide (38 aa) and A-chain (25 aa). Comparing with A. pectinifera RGP (ApeRGP), the amino acid identity levels between AmaRGP and ApeRGP were 58% for the A-chain and 73% for the B-chain. Furthermore, chemical synthetic AamRGP induced gamete spawning and oocyte maturation in ovarian fragments of A. amurensis. In contrast, the ovary of A. pectinifera failed to respond to the AamRGP. This suggested that AamRGP is a new relaxin-like peptide.

Duration of melatonin regulates seasonal plasticity in subtropical Indian weaver bird, Ploceus philippinus

Surbhi, ; Kumari, Yatinesh; Rani, Sangeeta; Tsutsui, Kazuyoshi; Kumar, Vinod

General and Comparative Endocrinology220p.46 - 542015年09月-2015年09月 

PubMedDOIScopus

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ISSN:00166480

概要:© 2014 Elsevier Inc. Day length regulates seasonal plasticity connected with reproduction in birds. Rhythmic pineal melatonin secretion is a reliable indicator of the night length, hence day length. Removal of rhythmic melatonin secretion by exposure to constant bright light (LLbright) or by pinealectomy renders several species of songbirds including Indian weaver bird (Ploceus philippinus) arrhythmic. Present study investigated whether rhythmic melatonin is involved in the regulation of key reproductive neuropeptides (GnRH I and GnIH) and reproduction linked neural changes, viz. song control nuclei, in Indian weaver birds. Two experiments were performed using birds in an arrhythmic condition with low (under LLbright) or no (in the absence of pineal gland) endogenous melatonin. In experiment I, three groups of birds (n=5 each) entrained to 12L:12D were exposed to LLbright (25lux) for two weeks. Beginning on day 15 of LLbright, a control group received vehicle for 16h and two treatment groups were given melatonin in drinking water for 8h or 16h. In experiment II, one group of sham-operated and three groups of pinealectomized birds (n=5 each) entrained to 12L:12D were exposed to constant dim light (LLdim, 0.5lux). Beginning on day 15 of LLdim, three groups received similar treatment as in experiment I. Birds were perfused after thirty cycles of the melatonin treatment, and brain sections were immunohistochemically double-labeled for GnRH I and GnIH or Nissl stained. Activity was recorded throughout the experiments, while body mass and testes were measured at the beginning and end of the experiment. Birds were synchronized with melatonin cycles and measured the duration of melatonin as "night". Pinealectomized birds that received 16h of melatonin had significantly higher GnIH-ir cells than those received 8h melatonin; there was no difference in the GnRH I immunoreactivity between two treatment groups however. Intact birds that received long duration melatonin cycles exhibited small song control nuclei, specifically the high vocal center (HVC) and the robust nucleus of the arcopallium (RA), while birds that received short duration melatonin or no melatonin exhibited large HVC and RA. Thus, melatonin possibly regulates seasonal reproduction via GnIH secretion, and also controls seasonal neuroplasticity in the song control system in songbirds.

GnIH and GnRH expressions in the central nervous system and pituitary of Indian major carp, Labeo rohita during ontogeny: An immunocytochemical study

Biswas, Saikat; Jadhao, Arun G.; Pinelli, Claudia; Palande, Nikhil V.; Tsutsui, Kazuyoshi

General and Comparative Endocrinology220p.88 - 922015年09月-2015年09月 

PubMedDOIScopus

詳細

ISSN:00166480

概要:© 2014 Elsevier Inc. Gonadotropin-releasing hormone (GnRH) is the major hypothalamic neuropeptide stimulating gonadotropin secretion in vertebrates. In 2000, gonadotropin-inhibitory hormone (GnIH) was discovered as a hypothalamic neuropeptide that inhibits gonadotropin secretion in birds. Subsequent studies have shown that GnIH is present in the brain of other vertebrates. We show for the first time GnIH immunoreactivity in the central nervous system and pituitary during development of Indian major carp, Labeo rohita and compare it with the localization of GnRH. GnIH and GnRH immunoreactivities were observed from the olfactory system to spinal cord throughout development. In the brain, both neuropeptides were localized in the telencephalon, diencephalon including the preoptic area and rhombencephalon. The localization of GnIH and GnRH in the pituitary suggests that these neuropeptides are involved in the regulation of pituitary hormones by an autocrine manner during development. In addition, the presence of GnIH and GnRH in several other brain regions including the olfactory system suggests their involvement in the regulation of other physiological functions.

A gonad-stimulating peptide of the crown-of-thorns starfish, Acanthaster planci

Mita, Masatoshi; Ikeda, Narumi; Haraguchi, Shogo; Tsutsui, Kazuyoshi; Nakano, Yoshikatsu; Nakamura, Masaru

Invertebrate Reproduction and Development2015年09月-2015年09月 

DOIScopus

詳細

ISSN:07924259

概要:© 2015 Taylor & Francis The crown-of thorns starfish, Acanthaster planci, has been blamed for coral mortality in a large number of coral reef systems in the Indo-Pacific region. Because population outbreaks of A. planci are closely related to reproduction, it is important to examine the mechanism of reproductive control in this starfish. Previously, a relaxin-like gonad-stimulating peptide (RGP) in starfish Asterina pectinifera has been identified as the gonadotropin responsible for final gamete maturation. On the basis of homology research on RGP cDNAs from several species, this study was carried out to identify gonadotropin in A. planci. The cDNA sequence of RGP was determined using a RACE product of mRNA from the radial nerves of A. planci. The coding DNA sequence consisted of 351 base pairs with an open reading frame encoding a peptide of 116 amino acids (aa), including a signal peptide (29 aa), B-chain (19 aa), C-peptide (44 aa), and A-chain (24 aa). The chemical structure of A. planci RGP was exactly the same as that of A. pectinifera RGP. Furthermore, synthetic RGP could induce gamete spawning and oocyte maturation in the ovarian fragments of A. planci. This strongly suggested that the RGP is a gonadotropin in A. planci.

Relaxin-like gonad-stimulating peptide is highly conserved in starfish Asterina pectinifera

Ikeda, Narumi; Uzawa, Haruka; Daiya, Misaki; Haraguchi, Shogo; Tsutsui, Kazuyoshi; Mita, Masatoshi

Invertebrate Reproduction and Development2015年09月-2015年09月 

DOIScopus

詳細

ISSN:07924259

概要:© 2015 Taylor & Francis Relaxin-like gonad-stimulating peptide (RGP) in starfish is the only known invertebrate peptide hormone responsible for final gamete maturation, rendering it functionally analogous to gonadotropins in vertebrates. Recently, RGP was purified from the radial nerves of starfish Asterina pectinifera, which belongs to the Order Valvatida in the Class Asteroidea. A. pectinifera is an endemic Japanese species, inhabiting rocky shores from northern to southern Japanese waters. This study examined whether genetic variation or polymorphism is found in RGP. Comparing cDNA sequences of RGP in A. pectinifera from 10 local populations in Japanese waters, we found that the coding DNA sequences (CDSs) were exactly the same. This result indicated that RGP is a highly conserved peptide in A. pectinifera. Furthermore, the CDS of RGP identified in Certonardoa semiregularis, which also belongs to Order Valvatida, was completely consistent with that of A. pectinifera. Thus, this also suggested that the chemical structure of A. pectinifera RGP is conserved among starfish of the Order Valvatida beyond species.

Food restriction negatively affects multiple levels of the reproductive axis in male house finches, Haemorhous mexicanus

Valle, Shelley; Carpentier, Elodie; Vu, Bethany; Tsutsui, Kazuyoshi; Deviche, Pierre

Journal of Experimental Biology218(17)p.2694 - 27042015年09月-2015年09月 

DOIScopus

詳細

ISSN:00220949

概要:© 2015. Published by The Company of Biologists Ltd. Nutrition influences reproductive functions across vertebrates, but the effects of food availability on the functioning of the hypothalamic- pituitary-gonadal (HPG) axis in wild birds and the mechanisms mediating these effects remain unclear.We investigated the influence of chronic food restriction on the HPG axis of photostimulated house finches, Haemorhous mexicanus. Food-restricted birds had underdeveloped testes with smaller seminiferous tubules than ad libitum-fed birds. Baseline plasma testosterone increased in response to photostimulation in ad libitum-fed but not in food-restricted birds. Food availability did not, however, affect the plasma testosterone increase resulting from a gonadotropin-releasing hormone-I (GnRH) or a luteinizing hormone (LH) challenge. The number of hypothalamic GnRH immunoreactive (ir) but not proGnRH-ir perikaryawas higher in food-restricted than in ad libitum-fed finches, suggesting inhibited secretion of GnRH. Hypothalamic gonadotropin-inhibitory hormone (GnIH)-ir and neuropeptide Y (NPY)-ir were not affected by food availability. Plasma corticosterone (CORT) was also not affected by food availability, indicating that the observed HPG axis inhibition did not result from increased activity of the hypothalamic-pituitary- adrenal (HPA) axis. This study is among the first to examine multilevel functional changes in the HPG axis in response to food restriction in a wild bird. The results indicate that food availability affects both hypothalamic and gonadal function, but further investigations are needed to clarify the mechanisms by which nutritional signals mediate these effects.

An Evolutionary Scenario for Gonadotrophin-Inhibitory Hormone in Chordates

Osugi, T.; Ubuka, T.; Tsutsui, K.

Journal of Neuroendocrinology27(6)p.556 - 5662015年01月-2015年01月 

DOIScopus

詳細

ISSN:09538194

概要:© 2014 British Society for Neuroendocrinology. In 2000, we discovered a novel hypothalamic neuropeptide that actively inhibits gonadotrophin release in quail and termed it gonadotrophin-inhibitory hormone (GnIH). GnIH peptides have subsequently been identified in most representative species of gnathostomes. They all share a C-terminal LPXRFamide (X = L or Q) motif. GnIH can inhibit gonadotrophin synthesis and release by decreasing the activity of GnRH neuroes, as well as by directly inhibiting pituitary gonadotrophin secretion in birds and mammals. To investigate the evolutionary origin of GnIH and its ancestral function, we identified a GnIH precursor gene encoding GnIHs from the brain of sea lamprey, the most ancient lineage of vertebrates. Lamprey GnIHs possess a C-terminal PQRFamide motif. In vivo administration of one of lamprey GnIHs stimulated the expression of lamprey GnRH in the hypothalamus and gonadotophin β mRNA in the pituitary. Thus, GnIH may have emerged in agnathans as a stimulatory neuropeptide that subsequently diverged to an inhibitory neuropeptide during the course of evolution from basal vertebrates to later-evolved vertebrates, such as birds and mammals. From a structural point of view, pain modulatory neuropeptides, such as neuropeptide FF (NPFF) and neuropeptide AF, share a C-terminal PQRFamide motif. Because agnathans possess both GnIH and NPFF genes, the origin of GnIH and NPFF genes may date back before the emergence of agnathans. More recently, we identified a novel gene encoding RFamide peptides in the amphioxus. Molecular phylogenetic analysis and synteny analysis indicated that this gene is closely related to the genes of GnIH and NPFF of vertebrates. The results suggest that the identified protochordate gene is similar to the common ancestor of GnIH and NPFF genes, indicating that the origin of GnIH and NPFF may date back to the time of the emergence of early chordates. The GnIH and NPFF genes may have diverged by whole-genome duplication during the course of vertebrate evolution.

Neuroanatomical Organization of the Brain Gonadotropin-Inhibitory Hormone and Gonadotropin-Releasing Hormone Systems in the Frog Pelophylax esculentus

Pinelli, Claudia;Jadhao, Arun G.;Biswas, Saikat P.;Tsutsui, Kazuyoshi;D'Aniello, Biagio

BRAIN BEHAVIOR AND EVOLUTION85(1)p.15 - 282015年-2015年

DOIWoS

詳細

ISSN:0006-8977

Low Temperature-Induced Circulating Triiodothyronine Accelerates Seasonal Testicular Regression

Ikegami, Keisuke;Atsumi, Yusuke;Yorinaga, Eriko;Ono, Hiroko;Murayama, Itaru;Nakane, Yusuke;Ota, Wataru;Arai, Natsumi;Tega, Akinori;Iigo, Masayuki;Darras, Veerle M.;Tsutsui, Kazuyoshi;Hayashi, Yoshitaka;Yoshida, Shosei;Yoshimura, Takashi

ENDOCRINOLOGY156(2)p.647 - 6592015年-2015年

DOIWoS

詳細

ISSN:0013-7227

Seasonal control of gonadotropin-inhibitory hormone (GnIH) in birds and mammals

Kriegsfeld, Lance J.;Ubuka, Takayoshi;Bentley, George E.;Tsutsui, Kazuyoshi

FRONTIERS IN NEUROENDOCRINOLOGY37p.65 - 752015年-2015年

DOIWoS

詳細

ISSN:0091-3022

社会的な刺激への生殖内分泌応答のメカニズム

戸張 靖子;筒井 和義

比較内分泌学41(155)p.68 - 702015年-2015年

CiNii

詳細

ISSN:1882-6636

A unique mechanism of successful fertilization in a domestic bird.

Sasanami Tomohiro;Izumi Shunsuke;Sakurai Naoki;Hirata Toshifumi;Mizushima Shusei;Matsuzaki Mei;Hiyama Gen;Yorinaga Eriko;Yoshimura Takashi;Ukena Kazuyoshi;Tsutsui Kazuyoshi

Scientific reports52015年-2015年

PubMedDOI

詳細

ISSN:2045-2322

概要::Fertilization is an indispensable step for formation of a zygote in sexual reproduction, leading to species survival. When mating occurs, sperm is transported to the female reproductive tracts via the seminal plasma (SP). SP is derived from male accessory sex glands and it plays pivotal roles for fertilization in animals. However, molecular mechanisms of SP or a fluid derived from male accessory sex glands for successful fertilization remain unclear. Here, we report that in male quail the cloacal gland (CG) produces prostaglandin F2α (PGF2α) that contributes to successful fertilization. PGF2α, as well as the secretion of CG (CGS), induced vaginal contractions and caused the opening of the entrance of the sperm storage tubules, the structures responsible for the long-term sperm storage and fertilization. The removal of CGS from the male before mating reduced the fertility, but the supplementation of CGS or PGF2α rescued the subfertility. We further showed that male CG contains glucose that is utilized as energy source for the intrinsic sperm mobility after transportation to female vagina. This mechanism, in concert with the excitatory effects of PGF2α enables successful fertilization in the domestic bird.

7α-Hydroxypregnenolone, a key neuronal modulator of locomotion, stimulates upstream migration by means of the dopaminergic system in salmon.

Haraguchi Shogo;Yamamoto Yuzo;Suzuki Yuko;Hyung Chang Joon;Koyama Teppei;Sato Miku;Mita Masatoshi;Ueda Hiroshi;Tsutsui Kazuyoshi

Scientific reports52015年-2015年

PubMedDOI

詳細

ISSN:2045-2322

概要::Salmon migrate upstream against an opposing current in their natal river. However, the molecular mechanisms that stimulate upstream migratory behavior are poorly understood. Here, we show that 7α-hydroxypregnenolone (7α-OH PREG), a newly identified neuronal modulator of locomotion, acts as a key factor for upstream migration in salmon. We first identified 7α-OH PREG and cytochrome P450 7α-hydroxylase (P4507α), a steroidogenic enzyme producing 7α-OH PREG, in the salmon brain and then found that 7α-OH PREG synthesis in the brain increases during upstream migration. Subsequently, we demonstrated that 7α-OH PREG increases upstream migratory behavior of salmon. We further found that 7α-OH PREG acts on dopamine neurons in the magnocellular preoptic nucleus during upstream migration. Thus, 7α-OH PREG stimulates upstream migratory behavior through the dopaminergic system in salmon. These findings provide new insights into the molecular mechanisms of fish upstream migration.

Review: Contribution of GnIH research to the progress of reproductive neuroendocrinology

K. Tsutsui, T. Ubuka, Y. L. Son, G. E. Bentley and L. J. Kriegsfeld

Front. Endocrinol.6(article 179)2015年-

DOI

Evolution of gonadotropin-inhibitory hormone receptor and its ligand

Ubuka, Takayoshi; Tsutsui, Kazuyoshi

General and Comparative Endocrinology209p.148 - 1612014年12月-2014年12月 

PubMedDOIScopus

詳細

ISSN:00166480

概要:© 2014 Elsevier Inc. Gonadotropin-inhibitory hormone (GnIH) is a neuropeptide inhibitor of gonadotropin secretion, which was first identified in the Japanese quail hypothalamus. GnIH peptides share a C-terminal LPXRFamide (X = L or Q) motif in most vertebrates. The receptor for GnIH (GnIHR) is the seven-transmembrane G protein-coupled receptor 147 (GPR147) that inhibits cAMP production. GPR147 is also named neuropeptide FF (NPFF) receptor 1 (NPFFR1), because it also binds NPFF that has a C-terminal PQRFamide motif. To understand the evolutionary history of the GnIH system in the animal kingdom, we searched for receptors structurally similar to GnIHR in the genome of six mammals (human, mouse, rat, cattle, cat, and rabbit), five birds (pigeon, chicken, turkey, budgerigar, and zebra finch), one reptile (green anole), one amphibian (Western clawed flog), six fishes (zebrafish, Nile tilapia, Fugu, coelacanth, spotted gar, and lamprey), one hemichordate (acorn worm), one echinoderm (purple sea urchin), one mollusk (California sea hare), seven insects (pea aphid, African malaria mosquito, honey bee, buff-tailed bumblebee, fruit fly, jewel wasp, and red flour beetle), one cnidarian (hydra), and constructed phylogenetic trees by neighbor joining (NJ) and maximum likelihood (ML) methods. A multiple sequence alignment of the receptors showed highly conserved seven-transmembrane domains as well as disulfide bridge sites between the first and second extracellular loops, including the receptor of hydra. Both NJ and ML analyses grouped the receptors of vertebrates into NPFFR1 and NPFFR2 (GPR74), and the receptors of insects into the receptor for SIFamide peptides that share a C-terminal YRKPPFNGSIFamide motif. Although human, quail and zebrafish GnIHR (NPFFR1) were most structurally similar to SIFamide receptor of fruit fly in the Famide peptide (FMRFamide, neuropeptide F, short neuropeptide F, drosulfakinin, myosuppressin, SIFamide) receptor families, the amino acid sequences and the peptide coding regions of GnIH precursors were most similar to FMRFamide precursor of fruit fly in the precursors of Famide peptide families. Chromosome synteny analysis of the precursor genes of human, quail and zebrafish GnIH and fruit fly Famide peptides further identified conserved synteny in vertebrate GnIH and fruit fly FMRFa precursor genes as well as other Famide peptide precursor genes. These results suggest that GnIH and its receptor pair and SIFamide and its receptor pair may have diverged and co-evolved independently in vertebrates and insects, respectively, from their ancestral Famide peptide and its receptor pair, during diversification and evolution of deuterostomian and protostomian species.

Breakthrough in neuroendocrinology by discovering novel neuropeptides and neurosteroids: 2. Discovery of neurosteroids and pineal neurosteroids

Tsutsui, Kazuyoshi; Haraguchi, Shogo

General and Comparative Endocrinology205p.11 - 222014年09月-2014年09月 

PubMedDOIScopus

詳細

ISSN:00166480

概要:© 2014 Elsevier Inc. Bargmann-Scharrer's discovery of "neurosecretion" in the first half of the 20th century has since matured into the scientific discipline of neuroendocrinology. Identification of novel neurohormones, such as neuropeptides and neurosteroids, is essential for the progress of neuroendocrinology. Our studies over the past two decades have significantly broadened the horizons of this field of research by identifying novel neuropeptides and neurosteroids in vertebrates that have opened new lines of scientific investigation in neuroendocrinology. We have established de novo synthesis and functions of neurosteroids in the brain of various vertebrates. Recently, we discovered 7α-hydroxypregnenolone (7α-OH PREG), a novel bioactive neurosteroid that acts as a key regulator for inducing locomotor behavior by means of the dopaminergic system. We further discovered that the pineal gland, an endocrine organ located close to the brain, is an important site of production of neurosteroids de novo from cholesterol (CHOL). The pineal gland secretes 7α-OH PREG and 3α,5α-tetrahydroprogesterone (3α,5α-THP; allopregnanolone) that are involved in locomotor rhythms and neuronal survival, respectively. Subsequently, we have demonstrated their mode of action and functional significance. This review summarizes the discovery of these novel neurosteroids and its contribution to the progress of neuroendocrinology.

Breakthrough in neuroendocrinology by discovering novel neuropeptides and neurosteroids: 1. Discovery of gonadotropin-inhibitory hormone (GnIH) across vertebrates

Tsutsui, Kazuyoshi; Ubuka, Takayoshi

General and Comparative Endocrinology205p.4 - 102014年09月-2014年09月 

PubMedDOIScopus

詳細

ISSN:00166480

概要:© 2014 Elsevier Inc. Bargmann-Scharrer's discovery of "neurosecretion" in the first half of the 20th century has since matured into the scientific discipline of neuroendocrinology. Identification of novel neurohormones, such as neuropeptides and neurosteroids, is essential for the progress of neuroendocrinology. Our studies over the past two decades have significantly broadened the horizons of this field of research by identifying novel neuropeptides and neurosteroids in vertebrates that have opened new lines of scientific investigation in neuroendocrinology. Since the discovery of gonadotropin-releasing hormone (GnRH) in mammals at the beginning of 1970s, it was generally believed that GnRH is the only hypothalamic neuropeptide regulating gonadotropin release in vertebrates. In 2000, however, we discovered a novel hypothalamic neuropeptide that actively inhibits gonadotropin release in quail and termed it gonadotropin-inhibitory hormone (GnIH). It now appears that GnIH is highly conserved across vertebrates, including humans, and serves a number of behavioral and physiological functions other than regulation of reproduction, providing enormous opportunity for investigators from a wide array of disciplines to study this neuropeptide. This review summarizes the discovery of GnIH and its contribution to the progress of neuroendocrinology.

Evolutionary origin of GnIH and NPFF in chordates: Insights from novel amphioxus RFamide peptides

Osugi, Tomohiro; Okamura, Tomoki; Son, You Lee; Ohkubo, Makoto; Ubuka, Takayoshi; Henmi, Yasuhisa; Tsutsui, Kazuyoshi

PLoS ONE9(7)2014年07月-2014年07月 

DOIScopus

詳細

概要:Gonadotropin-inhibitory hormone (GnIH) is a newly identified hypothalamic neuropeptide that inhibits pituitary hormone secretion in vertebrates. GnIH has an LPXRFamide (X = L or Q) motif at the C-terminal in representative species of gnathostomes. On the other hand, neuropeptide FF (NPFF), a neuropeptide characterized as a pain-modulatory neuropeptide, in vertebrates has a PQRFamide motif similar to the C-terminal of GnIH, suggesting that GnIH and NPFF have diverged from a common ancestor. Because GnIH and NPFF belong to the RFamide peptide family in vertebrates, protochordate RFamide peptides may provide important insights into the evolutionary origin of GnIH and NPFF. In this study, we identified a novel gene encoding RFamide peptides and two genes of their putative receptors in the amphioxus Branchiostoma japonicum. Molecular phylogenetic analysis and synteny analysis indicated that these genes are closely related to the genes of GnIH and NPFF and their receptors of vertebrates. We further identified mature RFamide peptides and their receptors in protochordates. The identified amphioxus RFamide peptides inhibited forskolin induced cAMP signaling in the COS-7 cells with one of the identified amphioxus RFamide peptide receptors expressed. These results indicate that the identified protochordate RFamide peptide gene is a common ancestral form of GnIH and NPFF genes, suggesting that the origin of GnIH and NPFF may date back to the time of the emergence of early chordates. GnIH gene and NPFF gene may have diverged by whole-genome duplication in the course of vertebrate evolution. © 2014 Osugi et al.

Biosynthesis and biological action of pineal allopregnanolone

Tsutsui, Kazuyoshi; Haraguchi, Shogo

Frontiers in Cellular Neuroscience8(MAY)2014年05月-2014年05月 

DOIScopus

詳細

ISSN:16625102

概要:The pineal gland transduces photoperiodic changes to the neuroendocrine system by rhythmic secretion of melatonin. We recently provided new evidence that the pineal gland is a major neurosteroidogenic organ and actively produces a variety of neurosteroids de novo from cholesterol in birds. Notably, allopregnanolone is a major pineal neurosteroid that is far more actively produced in the pineal gland than the brain and secreted by the pineal gland in juvenile birds. Subsequently, we have demonstrated the biological action of pineal allopregnanolone on Purkinje cells in the cerebellum during development in juvenile birds. Pinealectomy (Px) induces apoptosis of Purkinje cells, whereas allopregnanolone administration to Px chicks prevents cell death. Furthermore, Px increases the number of Purkinje cells that express active caspase-3, a crucial mediator of apoptosis, and allopregnanolone administration to Px chicks decreases the number of Purkinje cells expressing active caspase-3. It thus appears that pineal allopregnanolone prevents cell death of Purkinje cells by suppressing the activity of caspase-3 during development. This paper highlights new aspects of the biosynthesis and biological action of pineal allopregnanolone. © 2014 Tsutsui and Haraguchi.

Molecular evolution of GPCRs: 26Rfa/GPR103

Ukena, Kazuyoshi; Osugi, Tomohiro; Leprince, Jérôme; Vaudry, Hubert; Tsutsui, Kazuyoshi

Journal of Molecular Endocrinology52(3)p.T119 - T1312014年02月-2014年02月 

DOIScopus

詳細

ISSN:09525041

概要:Neuropeptides possessing the Arg-Phe-NH2 (RFamide) motif at their C-termini (designated as RFamide peptides) have been characterized in a variety of animals. Among these, neuropeptide 26RFa (also termed QRFP) is the latest member of the RFamide peptide family to be discovered in the hypothalamus of vertebrates. The neuropeptide 26RFa/QRFP is a 26-amino acid residue peptide that was originally identified in the frog brain. It has been shown to exert orexigenic activity in mammals and to be a ligand for the previously identified orphan G protein-coupled receptor, GPR103 (QRFPR). The cDNAs encoding 26RFa/QRFP and QRFPR have now been characterized in representative species of mammals, birds, and fish. Functional studies have shown that, in mammals, the 26RFa/QRFP-QRFPR system may regulate various functions, including food intake, energy homeostasis, bone formation, pituitary hormone secretion, steroidogenesis, nociceptive transmission, and blood pressure. Several biological actions have also been reported in birds and fish. This review summarizes the current state of identification, localization, and understanding of the functions of 26RFaQRFP and its cognate receptor, QRFPR, in vertebrates. © 2014 Society for Endocrinology.

Hypothalamic inhibition of socio-sexual behaviour by increasing neuroestrogen synthesis

Ubuka, Takayoshi; Haraguchi, Shogo; Tobari, Yasuko; Narihiro, Misato; Ishikawa, Kei; Hayashi, Takanori; Harada, Nobuhiro; Tsutsui, Kazuyoshi

Nature Communications52014年01月-2014年01月 

DOIScopus

詳細

概要:Gonadotropin-inhibitory hormone (GnIH) is a hypothalamic neuropeptide that inhibits gonadotropin secretion and socio-sexual behaviours. Oestrogen (neuroestrogen) synthesized in the brain from androgen by aromatase regulates male socio-sexual behaviours. Here we show that GnIH directly activates aromatase and increases neuroestrogen synthesis in the preoptic area (POA) and inhibits socio-sexual behaviours of male quail. Aromatase activity and neuroestrogen concentration in the POA are low in the morning when the birds are active, but neuroestrogen synthesis gradually increases until the evening when the birds become inactive. Centrally administered GnIH in the morning increases neuroestrogen synthesis in the POA and decreases socio-sexual behaviours. Centrally administered 17β-oestradiol at higher doses also inhibits socio-sexual behaviours in the morning. These results suggest that GnIH inhibits male socio-sexual behaviours by increasing neuroestrogen synthesis beyond its optimum concentration for the expression of socio-sexual behaviours. This is the first demonstration of any hypothalamic neuropeptide that directly regulates neuroestrogen synthesis. © 2014 Macmillan Publishers Limited. All rights reserved.

Central and direct regulation of testicular activity by gonadotropin-inhibitory hormone and its receptor

Ubuka, Takayoshi; Son, You Lee; Tobari, Yasuko; Narihiro, Misato; Bentley, George E.; Kriegsfeld, Lance J.; Tsutsui, Kazuyoshi

Frontiers in Endocrinology5(JAN)2014年01月-2014年01月 

Scopus

詳細

概要:Gonadotropin-inhibitory hormone (GnIH) was first identified in Japanese quail to be an inhibitor of gonadotropin synthesis and release. GnIH peptides have since been identified in all vertebrates, and all share an LPXRFamide (X = L or Q) motif at their C-termini. The receptor for GnIH is the G protein-coupled receptor 147 (GPR147), which inhibits cAMP signaling. Cell bodies of GnIH neurons are located in the paraventricular nucleus (PVN) in birds and the dorsomedial hypothalamic area (DMH) in most mammals. GnIH neurons in the PVN or DMH project to the median eminence to control anterior pituitary function via GPR147 expressed in gonadotropes. Further, GnIH inhibits gonadotropin-releasing hormone (GnRH)-induced gonadotropin subunit gene transcription by inhibiting the adenylate cyclase/cAMP/PKA-dependent ERK pathway in an immortalized mouse gonadotrope cell line (LβT2 cells). GnIH neurons also project to GnRH neurons that express GPR147 in the preoptic area (POA) in birds and mammals. Accordingly, GnIH can inhibit gonadotropin synthesis and release by decreasing the activity of GnRH neurons as well as by directly inhibiting pituitary gonadotrope activity. GnIH and GPR147 can thus centrally suppress testosterone secretion and spermatogenesis by acting in the hypothalamic-pituitary-gonadal axis. GnIH and GPR147 are also expressed in the testis of birds and mammals, possibly acting in an autocrine/paracrine manner to suppress testosterone secretion and spermatogenesis. GnIH expression is also regulated by melatonin, stress, and social environment in birds and mammals. Accordingly, the GnIH-GPR147 system may play a role in transducing physical and social environmental information to regulate optimal testicular activity in birds and mammals. This review discusses central and direct inhibitory effects of GnIH and GPR147 on testosterone secretion and spermatogenesis in birds and mammals. © 2014 Ubuka, Son, Tobari, Narihiro, Bentley, Kriegsfeld and Tsutsui.

Molecular basis for the activation of gonadotropin-inhibitory hormone gene transcription by corticosterone

Son, You Lee; Ubuka, Takayoshi; Narihiro, Misato; Fukuda, Yujiro; Hasunuma, Itaru; Yamamoto, Kazutoshi; Belsham, Denise D.; Tsutsui, Kazuyoshi

Endocrinology155(5)p.1817 - 18262014年01月-2014年01月 

PubMedDOIScopus

詳細

ISSN:00137227

概要:The inhibitory effect of stress on reproductive function is potentially mediated by high concentrations of circulating glucocorticoids (GCs) acting via the GC receptor (GR). Gonadotropin-inhibitory hormone (GnIH) is a hypothalamic neuropeptide that inhibits gonadotropin secretion. GnIH may mediate stress-induced reproductive dysfunction. However, it is not yet known whether GCbound GR is directly involved in GnIH transcription. Here, we demonstrated the localization of GR mRNA in GnIH neurons in the paraventricular nucleus of quail, suggesting that GC can directly regulate GnIH transcription. We next showed that 24 hours of treatment with corticosterone (CORT) increase GnIH mRNA expression in the quail diencephalon. We further investigated the mechanism of activation of GnIH transcription by CORT using a GnIH-expressing neuronal cell line, rHypoE-23, derived from rat hypothalamus. We found the expression of GR mRNA in rHypoE-23 cells and increased GnIHmRNAexpression by 24 hours of CORT treatment.Wefinally characterized the promoter activity of rat GnIH gene stimulated by CORT. Through DNA deletion analysis, we identified a CORT-responsive region at 2000-1501 bp upstream of GnIH precursor coding region. This region included 2 GC response elements (GREs) at -1665 and -1530 bp. Mutation of -1530 GRE abolished CORT responsiveness. We also found CORT-stimulated GR recruitment at the GnIH promoter region containing the -1530 GRE. These results provide a putative molecular basis for transcriptional activation of GnIH under stress by demonstrating that CORT directly induces GnIH transcription by recruitment of GR to its promoter. © 2014 by the Endocrine Society.

A new pathway mediating social effects on the endocrine system: Female presence acting via norepinephrine release stimulates gonadotropin-inhibitory hormone in the paraventricular nucleus and suppresses luteinizing hormone in quail

Tobari, Yasuko; Son, You Lee; Ubuka, Takayoshi; Hasegawa, Yoshihisa; Tsutsui, Kazuyoshi

Journal of Neuroscience34(29)p.9803 - 98112014年01月-2014年01月 

PubMedDOIScopus

詳細

ISSN:02706474

概要:Rapid effects of social interactions on transient changes in hormonal levels are known in a wide variety of vertebrate taxa, ranging from fish to humans. Although these responses are mediated by the brain, neurochemical pathways that translate social signals into reproductive physiological changes are unclear. In this study, we analyzed how a female presence modifies synthesis and/or release of various neurochemicals, such as monoamines and neuropeptides, in the brain and downstream reproductive hormones in sexually active male Japanese quail. By viewing a female bird, sexually active males rapidly increased norepinephrine (NE) release in the paraventricular nucleus (PVN) of the hypothalamus, in which gonadotropin-inhibitory hormone (GnIH) neuronal cell bodies exist, increased GnIH precursor mRNA expression in the PVN, and decreased luteinizing hormone (LH) concentration in the plasma. GnIH is a hypothalamic neuropeptide that inhibits gonadotropin secretion from the pituitary. It was further shown that GnIH can rapidly suppress LH release after intravenous administration in this study. Centrally administered NE decreased plasma LH concentration in vivo. It was also shown that NE stimulated the release of GnIH from diencephalic tissue blocks in vitro. Fluorescence double-label immunohistochemistry indicated that GnIH neurons received noradrenergic innervations, and immunohistochemistry combined with in situ hybridization have further shown that GnIH neurons expressed α2A-adrenergic receptor mRNA. These results indicate that a female presence increases NE release in the PVN and stimulates GnIH release, resulting in the suppression of LH release in sexually active male quail. © 2014 the authors.

Review: Evolution of GnIH and related peptides structure and function in the chordates

Osugi, Tomohiro; Osugi, Tomohiro; Ubuka, Takayoshi; Tsutsui, Kazuyoshi

Frontiers in Neuroscience(8 JUL)2014年01月-2014年01月 

DOIScopus

詳細

ISSN:16624548

概要:Discovery of gonadotropin-inhibitory hormone (GnIH) in the Japanese quail in 2000 was the first to demonstrate the existence of a hypothalamic neuropeptide inhibiting gonadotropin release. We now know that GnIH regulates reproduction by inhibiting gonadotropin synthesis and release via action on the gonadotropin-releasing hormone (GnRH) system and the gonadotrope in various vertebrates. GnIH peptides identified in birds and mammals have a common LPXRF-amide (X = L or Q) motif at the C-terminus and inhibit pituitary gonadotropin secretion. However, the function and structure of GnIH peptides are diverse in fish. Goldfish GnIHs possessing a C-terminal LPXRF-amide motif have both stimulatory and inhibitory effects on gonadotropin synthesis or release. The C-terminal sequence of grass puffer and medaka GnIHs are MPQRF-amide. To investigate the evolutionary origin of GnIH and its ancestral structure and function, we searched for GnIH in agnathans, the most ancient lineage of vertebrates. We identified GnIH precursor gene and mature GnIH peptides with C-terminal QPQRF-amide or RPQRF-amide from the brain of sea lamprey. Lamprey GnIH fibers were in close proximity to GnRH-III neurons. Further, one of lamprey GnIHs stimulated the expression of lamprey GnRH-III peptide in the hypothalamus and gonadotropic hormone ß mRNA expression in the pituitary. We further identified the ancestral form of GnIH, which had a C-terminal RPQRF-amide, and its receptors in amphioxus, the most basal chordate species. The amphioxus GnIH inhibited cAMP signaling in vitro. In sum, the original forms of GnIH may date back to the time of the emergence of early chordates. GnIH peptides may have had various C-terminal structures slightly different from LPXRF-amide in basal chordates, which had stimulatory and/or inhibitory functions on reproduction. The C-terminal LPXRF-amide structure and its inhibitory function on reproduction may be selected in later-evolved vertebrates, such as birds and mammals.

Review: Neuroestrogen regulation of socio-sexual behavior of males

Ubuka, Takayoshi; Tsutsui, Kazuyoshi

Frontiers in Neuroscience8(OCT)2014年01月-2014年01月 

DOIScopus

詳細

ISSN:16624548

概要:© 2014 Ubuka and Tsutsui. It is thought that estrogen (neuroestrogen) synthesized by the action of aromatase in the brain from testosterone activates male socio-sexual behaviors, such as aggression and sexual behavior in birds. We recently found that gonadotropin-inhibitory hormone (GnIH), a hypothalamic neuropeptide, inhibits socio-sexual behaviors of male quail by directly activating aromatase and increasing neuroestrogen synthesis in the preoptic area (POA). The POA is thought to be the most critical site of aromatization and neuroestrogen action for the regulation of socio-sexual behavior of male birds. We concluded that GnIH inhibits socio-sexual behaviors of male quail by increasing neuroestrogen concentration beyond its optimal concentration in the brain for expression of socio-sexual behavior. On the other hand, it has been reported that dopamine and glutamate, which stimulate male socio-sexual behavior in birds and mammals, inhibit the activity of aromatase in the POA. Multiple studies also report that the activity of aromatase or neuroestrogen is negatively correlated with changes in male socio-sexual behavior in fish, birds, and mammals including humans. Here, we review previous studies that investigated the role of neuroestrogen in the regulation of male socio-sexual behavior and reconsider the hypothesis that neuroestrogen activates male socio-sexual behavior in vertebrates. It is considered that basal concentration of neuroestrogen is required for the maintenance of male socio-sexual behavior but higher concentration of neuroestrogen may inhibit male socio-sexual behavior.

Inhibitory roles of the mammalian GnIH ortholog RFRP3 in testicular activities in adult mice

Anjum, Shabana;Krishna, Amitabh;Tsutsui, Kazuyoshi

JOURNAL OF ENDOCRINOLOGY223(1)p.79 - 912014年-2014年

DOIWoS

詳細

ISSN:0022-0795

Gonadotropin-inhibitory hormone inhibits aggressive behavior of male quail by increasing neuroestrogen synthesis in the brain beyond its optimum concentration

Ubuka, Takayoshi;Tsutsui, Kazuyoshi

GENERAL AND COMPARATIVE ENDOCRINOLOGY205p.49 - 542014年-2014年

DOIWoS

詳細

ISSN:0016-6480

Involvement of G alpha s-proteins in the action of relaxin-like gonad-stimulating substance on starfish ovarian follicle cells

Mita, Masatoshi;Haraguchi, Shogo;Watanabe, Miho;Takeshige, Yuki;Yamamoto, Kazutoshi;Tsutsui, Kazuyoshi

GENERAL AND COMPARATIVE ENDOCRINOLOGY205p.80 - 872014年-2014年

DOIWoS

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ISSN:0016-6480

Gonadotropin-inhibitory hormone-stimulation of food intake is mediated by hypothalamic effects in chicks

McConn, Betty;Wang, Guoqing;Yi, Jiaqing;Gilbert, Elizabeth R.;Osugi, Tomohiro;Ubuka, Takayoshi;Tsutsui, Kazuyoshi;Chowdhury, Vishwajit S.;Furuse, Mitsuhiro;Cline, Mark A.

NEUROPEPTIDES48(6)p.327 - 3342014年-2014年

DOIWoS

詳細

ISSN:0143-4179

Differential expressions of RFamide-related peptide, a mammalian gonadotropin-inhibitory hormone ortholog, and kisspeptin in the hypothalamus of Abadeh ecotype does during breeding and anestrous seasons

M. R. J. Shirazi, M. J. Zamiri, M. S. Salehi, S. Moradi, A. Tamadon, M. R. Namavar, A. Akhlaghi, K. Tsutsui and A. Caraty

J. Neuroendocrinol.26p.186 - 1942014年-

Molecular evolution of Kiss2 genes and peptides in vertebrates

Osugi, Tomohiro; Ohtaki, Naohito; Sunakawa, Yuya; Son, You Lee; Ohkubo, Makoto; Iigo, Masayuki; Amano, Masafumi; Tsutsui, Kazuyoshi

Endocrinology154(11)p.4270 - 42802013年11月-2013年11月 

PubMedDOIScopus

詳細

ISSN:00137227

概要:The kiss1 peptide (kisspeptin), a product of the kiss1 gene, is one of the key neuropeptides regulating vertebrate reproduction. In 2009, we identified a paralogous gene of kiss1 in the brain of amphibians and named it kiss2. Currently, the presence of the kiss2 gene and the kiss2 peptide is still obscure in amniotes compared with that in other vertebrates. Therefore, we performed genomedatabase analyses in primates and reptiles to investigate the molecular evolution of the kiss2 gene in vertebrates. Because the mature kiss2 peptide has been identified only in amphibians, we further performed immunoaffinity purification and mass spectrometry to identify the mature endogenous kiss2 peptide in the brains of salmon and turtle that possessed the kiss2 gene. Here we provide the first evidence for the presence of a kiss2-like gene in the genome database of primates including humans. Synthetic amidated human KISS2 peptide activated human GPR54 expressed in COS7 cells, but nonamidated KISS2 peptide was inactive. The endogenous amidated kiss2 peptide may not be produced in primates because of the lack of an amidation signal in the precursor polypeptide. The kiss2-like gene may be nonfunctional in crocodilians because of premature stop codons. We identified the mature amidated kiss2 peptide in turtles and fish and analyzed the localization of kiss2 peptidemRNAexpression in fish. The present study suggests that the kiss2 gene may have mutated in primates and crocodilians and been lost in birds during the course of evolution. In contrast, the kiss2 gene and mature kiss2 peptide are present in turtles and fish. Copyright © 2013 by The Endocrine Society.

Biosynthesis and biological actions of pineal neurosteroids in domestic birds

Tsutsui, Kazuyoshi; Haraguchi, Shogo; Hatori, Megumi; Hatori, Megumi; Hirota, Tsuyoshi; Hirota, Tsuyoshi; Fukada, Yoshitaka

Neuroendocrinology98(2)p.97 - 1052013年10月-2013年10月 

PubMedDOIScopus

詳細

ISSN:00283835

概要:The central and peripheral nervous systems have the capacity of synthesizing steroids de novo from cholesterol, the so-called 'neurosteroids'. De novo synthesis of neurosteroids from cholesterol appears to be a conserved property across the subphylum vertebrata. Until recently, it was generally believed that neurosteroids are produced in neurons and glial cells in the central and peripheral nervous systems. However, our recent studies on birds have demonstrated that the pineal gland, an endocrine organ located close to the brain, is an important site of production of neurosteroids de novo from cholesterol. 7α-Hydroxypregnenolone is a major pineal neurosteroid that stimulates locomotor activity of juvenile birds, connecting light-induced gene expression with locomotion. The other major pineal neurosteroid allopregnanolone is involved in Purkinje cell survival by suppressing the activity of caspase-3, a crucial mediator of apoptosis during cerebellar development. This review is an updated summary of the biosynthesis and biological actions of pineal neurosteroids. © 2013 S. Karger AG, Basel.

Brain and pineal 7α-hydroxypregnenolone stimulating locomotor activity: Identification, mode of action and regulation of biosynthesis

Tsutsui, Kazuyoshi; Haraguchi, Shogo; Fukada, Yoshitaka; Vaudry, Hubert

Frontiers in Neuroendocrinology34(3)p.179 - 1892013年08月-2013年08月 

DOIScopus

詳細

ISSN:00913022

概要:Biologically active steroids synthesized in the central and peripheral nervous systems are termed neurosteroids. However, the biosynthetic pathways leading to the formation of neurosteroids are still incompletely elucidated. 7α-Hydroxypregnenolone, a novel bioactive neurosteroid stimulating locomotor activity, has been recently identified in the brain of newts and quail. Subsequently, the mode of action and regulation of biosynthesis of 7α-hydroxypregnenolone have been determined. Moreover, recent studies on birds have demonstrated that the pineal gland, an endocrine organ located close to the brain, is an important site of production of neurosteroids de novo from cholesterol. 7α-Hydroxypregnenolone is a major pineal neurosteroid that stimulates locomotor activity in juvenile chickens, connecting light-induced gene expression with locomotion. This review summarizes the advances in our understanding of the identification, mode of action and regulation of biosynthesis of brain and pineal 7α-hydroxypregnenolone, a potent stimulator of locomotor activity. © 2013 Elsevier Inc.

Review: Regulatory mechanisms of gonadotropin-inhibitory hormone (GnIH) synthesis and release in photoperiodic animals

Tsutsui, Kazuyoshi; Ubuka, Takayoshi; Bentley, George E.; Kriegsfeld, Lance J.

Frontiers in Neuroscience7 APR(article 38)p.1 - 112013年06月-2013年06月 

DOIScopus

詳細

ISSN:16624548

概要:Gonadotropin-inhibitory hormone (GnIH) is a novel hypothalamic neuropeptide that was discovered in quail as an inhibitory factor for gonadotropin release. GnIH inhibits gonadotropin synthesis and release in birds through actions on gonadotropin-releasing hormone (GnRH) neurons and gonadotropes, mediated via the GnIH receptor (GnIH-R), GPR147. Subsequently, GnIH was identified in mammals and other vertebrates. As in birds, mammalian GnIH inhibits gonadotropin secretion, indicating a conserved role for this neuropeptide in the control of the hypothalamic-pituitary-gonadal (HPG) axis across species. Identification of the regulatory mechanisms governing GnIH expression and release is important in understanding the physiological role of the GnIH system. A nocturnal hormone, melatonin, appears to act directly on GnIH neurons through its receptor to induce expression and release of GnIH in quail, a photoperiodic bird. Recently, a similar, but opposite, action of melatonin on the inhibition of expression of mammalian GnIH was shown in hamsters and sheep, photoperiodic mammals. These results in photoperiodic animals demonstrate that GnIH expression is photoperiodically modulated via a melatonin-dependent process. Recent findings indicate that GnIH may be a mediator of stress-induced reproductive disruption in birds and mammals, pointing to a broad role for this neuropeptide in assessing physiological state and modifying reproductive effort accordingly. This paper summarizes the advances made in our knowledge regarding the regulation of GnIH synthesis and release in photoperiodic birds and mammals. This paper also discusses the neuroendocrine integration of environmental signals, such as photoperiods and stress, and internal signals, such as GnIH, melatonin, and glucocorticoids, to control avian and mammalian reproduction. © 2013 Tsutsui, Ubuka, Bentley and Kriegsfeld.

New biosynthesis and biological actions of avian neurosteroids

Tsutsui, Kazuyoshi; Haraguchi, Shogo; Inoue, Kazuhiko; Miyabara, Hitomi; Ubuka, Takayoshi; Hatori, Megumi; Hirota, Tsuyoshi; Hirota, Tsuyoshi; Fukada, Yoshitaka

Journal of Experimental Neuroscience7(1)p.15 - 292013年06月-2013年06月 

DOIScopus

詳細

概要:De novo neurosteroidogenesis from cholesterol occurs in the brain of various avian species. However, the biosynthetic pathways leading to the formation of neurosteroids are still not completely elucidated. We have recently found that the avian brain produces 7a-hydroxypregnenolone, a novel bioactive neurosteroid that stimulates locomotor activity. Until recently, it was believed that neurosteroids are produced in neurons and glial cells in the central and peripheral nervous systems. However, our recent studies on birds have demonstrated that the pineal gland, an endocrine organ located close to the brain, is an important site of production of neurosteroids de novo from cholesterol. 7a-Hydroxypregnenolone is a major pineal neurosteroid that stimulates locomotor activity of juvenile birds, connecting light-induced gene expression with locomotion. The other major pineal neurosteroid allopregnanolone is involved in Purkinje cell survival during development. This paper highlights new aspects of neurosteroid synthesis and actions in birds. © The author(s), publisher and licensee Libertas Academica Ltd.

Review: Gonadotropin-inhibitory hormone (GnIH), GnIH receptor and cell signaling.

T. Ubuka, Y.L. Son, G.E. Bentley, R.P. Millar, K. Tsutsui.

Gen. Comp. Endocrinol.(190)p.10 - 172013年03月-

DOI

Identification, localization and function of a novel neuropeptide, 26RFa, and its cognate receptor, GPR103, in the avian hypothalamus

Ukena, Kazuyoshi;Tachibana, Tetsuya;Tobari, Yasuko;Leprince, Jerome;Vaudry, Hubert;Tsutsui, Kazuyoshi

GENERAL AND COMPARATIVE ENDOCRINOLOGY190p.42 - 462013年03月-2013年03月 

DOIWoS

詳細

ISSN:0016-6480

Review: Melatonin stimulates the synthesis and release of gonadotropin-inhibitory hormone in birds

Chowdhury, Vishwajit S.; Ubuka, Takayoshi; Tsutsui, Kazuyoshi

General and Comparative Endocrinology181(1)p.175 - 1782013年01月-2013年01月 

PubMedDOIScopus

詳細

ISSN:00166480

概要:Gonadotropin-inhibitory hormone (GnIH), a neuropeptide that inhibits gonadotropin synthesis and release, was first identified in the quail hypothalamus. To understand the physiological role of GnIH, this review will demonstrate the mechanisms that regulate GnIH synthesis and release. Pinealectomy (Px) combined with orbital enucleation (Ex) decreased the synthesis of GnIH precursor mRNA and content of mature GnIH peptide in the diencephalon. Melatonin administration to Px plus Ex birds caused a dose-dependent increase in the synthesis of GnIH precursor mRNA and production of mature peptide. A melatonin receptor subtype, Mel1c, was expressed in GnIH-immunoreactive neurons, suggesting direct action of melatonin on GnIH neurons. Melatonin administration further increased GnIH release in a dose-dependent manner from hypothalamic explants in vitro. GnIH mRNA expression and GnIH release during the dark period were greater than those during the light period in explants from quail exposed to long-day photoperiods. Conversely, plasma luteinizing hormone (LH) concentration decreased during the dark period. This review summarizes that melatonin appears to act on GnIH neurons in stimulating not only GnIH synthesis but also its release, thus inhibiting plasma LH concentration in birds. © 2012 Elsevier Inc.

Create new research directions in comparative endocrinology from Asia and Oceania

Tsutsui, Kazuyoshi

General and Comparative Endocrinology181(1)p.192 - 1962013年01月-2013年01月 

PubMedDOIScopus

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ISSN:00166480

概要:The Asia and Oceania Society for Comparative Endocrinology (AOSCE) was founded in 1987, when the first congress was held in Nagoya, Japan. The purpose of the AOSCE is to progress scientific activities in the field of comparative endocrinology in Asia and Oceania and to establish a deep relationship among the members. For this purpose, the AOSCE holds a congress or an intercongress symposium every 2. years, which organizes an attractive scientific program covering the latest progress in the broad aspect of comparative endocrinology. 2012 was the 25th anniversary of AOSCE. Our scientific activities have increased dramatically during the past 25. years. The 7th AOSCE congress was held in Kuala Lumpur, Malaysia in 2012. The theme of this congress was " Overcoming challenges in the 21st century" To overcome challenges in the 21st century, we further need to create new research directions in comparative endocrinology from Asia and Oceania. This paper describes a brief history of the AOSCE and also highlights the discovery of gonadotropin-inhibitory hormone (GnIH) and the progress of GnIH research as one of new research directions in comparative endocrinology. In 2000, GnIH was discovered in Japan and now more than 50 laboratories are working on GnIH in the world. The discovery of GnIH has changed our understanding about regulation of the reproductive axis drastically in the past decade. © 2012 Elsevier Inc.

A genetically female brain is required for a regular reproductive cycle in chicken brain chimeras.

F. Maekawa, M. Sakurai, Y. Yamashita, K. Tanaka, S. Haraguchi, K. Yamamoto, K. Tsutsui, H. Yoshioka, S. Murakami, R. Tadano, T. Goto, J. Shiraishi, K. Tomonari, T. Oka, K. Ohara, T. Maeda, T. Bungo, M. Tsudzuki and H. Ohki-Hamazaki

Nat. Commun.4p.1372 - 13722013年-

DOI

Review: Regulatory mechanisms of gonadotropin-inhibitory hormone (GnIH) synthesis and release in photoperiodic animals.

K. Tsutsui, T. Ubuka, G. E. Bentley and L. Kriegsfeld

Front. Endocrinol.3, Article 126p.1 - 112013年-

DOI

Review: Neuroendocrine regulation of gonadotropin secretion in seasonally breeding birds.

T. Ubuka, G. E. Bentley and K. Tsutsui

Front. Endocrinol.7, Article38p.1 - 172013年-

DOI

10th International Symposium on Avian Endocrinology

Tsutsui, Kazuyoshi;Sharp, Peter J.;Dores, Robert M.

GENERAL AND COMPARATIVE ENDOCRINOLOGY190p.1 - 22013年-2013年

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ISSN:0016-6480

Biosynthesis and Biological Actions of Pineal Neurosteroids in Domestic Birds

Tsutsui, Kazuyoshi;Haraguchi, Shogo;Hatori, Megumi;Hirota, Tsuyoshi;Fukada, Yoshitaka

NEUROENDOCRINOLOGY98(2)p.97 - 1052013年-2013年

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詳細

ISSN:0028-3835

Contribution of de novo synthesis of G alpha s-proteins to 1-methyladenine production in starfish ovarian follicle cells stimulated by relaxin-like gonad-stimulating substance

Mita, Masatoshi;Haraguchi, Shogo;Uzawa, Haruka;Tsutsui, Kazuyoshi

BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS440(4)p.798 - 8012013年-2013年

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ISSN:0006-291X

Review: Neuroendocrine regulation of gonadotropin secretion in seasonally breeding birds

Ubuka, Takayoshi;Bentley, George E.;Tsutsui, Kazuyoshi

FRONTIERS IN NEUROSCIENCE7(article38)p.1 - 112013年-2013年

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ISSN:1662-453X

Contribution of Leydig and Sertoli Cells to Testosterone Production in Mouse Fetal Testes

Shima, Yuichi;Miyabayashi, Kanako;Haraguchi, Shogo;Arakawa, Tatsuhiko;Otake, Hiroyuki;Baba, Takashi;Matsuzaki, Sawako;Shishido, Yurina;Akiyama, Haruhiko;Tachibana, Taro;Tsutsui, Kazuyoshi;Morohashi, Ken-ichirou

MOLECULAR ENDOCRINOLOGY27(1)p.63 - 732013年-2013年

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ISSN:0888-8809

RNA interference of gonadotropin-inhibitory hormone gene induces aggressive and sexual behaviors in birds

Ubuka, Takayoshi;Mizuno, Takanobu;Fukuda, Yujiro;Bentley, George E.;Wingfield, John C.;Tsutsui, Kazuyoshi

GENERAL AND COMPARATIVE ENDOCRINOLOGY181p.179 - 1862013年-2013年

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ISSN:0016-6480

Olfactory response to the abdominal gland-derived steroids in the newt, Cynops pyrrhogaster

Toyoda, Fumiyo;Nakada, Tomoaki;Haraguchi, Shogo;Yamamoto, Kazutoshi;Tsutsui, Kazuyoshi;Yamashita, Masayuki;Kikuyama, Sakae

JOURNAL OF PHYSIOLOGICAL SCIENCES63p.S214 - S2142013年-2013年

WoS

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ISSN:1880-6546

Brain and pineal 7α-hydroxypregnenolone stimulating locomotor activity: Identification, mode of action and regulation of biosynthesis

Tsutsui, Kazuyoshi;Haraguchi, Shogo;Fukada, Yoshitaka;Vaudry, Hubert

FRONTIERS IN NEUROENDOCRINOLOGY34(3)p.179 - 1892013年-2013年

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ISSN:0091-3022

Gonadotropin-inhibitory hormone reduces sexual motivation but not lordosis behavior in female Syrian hamsters (Mesocricetus auratus)

Piekarski, David J.;Zhao, Sheng;Jennings, Kimberly J.;Iwasa, Takeshi;Legan, Sandra J.;Mikkelsen, Jens D.;Tsutsui, Kazuyoshi;Kriegsfeld, Lance J.

HORMONES AND BEHAVIOR64(3)p.501 - 5102013年-2013年

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ISSN:0018-506X

Molecular Evolution of Kiss2 Genes and Peptides in Vertebrates

Osugi, Tomohiro;Ohtaki, Naohito;Sunakawa, Yuya;Son, You Lee;Ohkubo, Makoto;Iigo, Masayuki;Amano, Masafumi;Tsutsui, Kazuyoshi

ENDOCRINOLOGY154(11)p.4270 - 42802013年-2013年

DOIWoS

詳細

ISSN:0013-7227

Expression of RFamide-related peptide in the dorsomedial nucleus of hypothalamus during the estrous cycle of rats.

M. R. J. Shirazi, F. Pazoohi, M. J. Zamiri, M. S. Salehi, M. R. Namavar, A. Tamadon, N. Tanideh, A. Zarei and K. Tsutsui

Physiol. Pharmacol.17p.72 - 792013年-

Possible role of pineal allopregnanolone in Purkinje cell survival

Haraguchi, Shogo; Hara, Sakurako; Ubuka, Takayoshi; Mita, Masatoshi; Tsutsui, Kazuyoshi

Proceedings of the National Academy of Sciences of the United States of America109(51)p.21110 - 211152012年12月-2012年12月 

PubMedDOIScopus

詳細

ISSN:00278424

概要:It is believed that neurosteroids are produced in the brain and other nervous systems. Here, we show that allopregnanolone (ALLO), a neurosteroid, is exceedingly produced in the pineal gland compared with the brain and that pineal ALLO acts on the Purkinje cell, a principal cerebellar neuron, to prevent apoptosis in the juvenile quail. We first demonstrated that the pineal gland is a major organ of neurosteroidogenesis. A series of experiments using molecular and biochemical techniques has further demonstrated that the pineal gland produces a variety of neurosteroids de novo from cholesterol in the juvenile quail. Importantly, ALLO was far more actively produced in the pineal gland than in the brain. Pinealectomy (Px) decreased ALLO concentration in the cerebellum and induced apoptosis of Purkinje cells, whereas administration of ALLO to Px quail chicks prevented apoptosis of Purkinje cells.We further found that Px significantly increased the number of Purkinje cells that expressed active caspase-3, a key protease in apoptotic pathway, and daily injection of ALLO to Px quail chicks decreased the number of Purkinje cells expressing active caspase-3. These results indicate that the neuroprotective effect of pineal ALLO is associated with the decrease in caspase-3 activity during the early stage of neuronal development. We thus provide evidence that the pineal gland is an important neurosteroidogenic organ and that pineal ALLO may be involved in Purkinje cell survival during development. This is an important function of the pineal gland in the formation of neuronal circuits in the developing cerebellum.

Review: Gonadotropin-inhibitory hormone action in the brain and pituitary

Ubuka, Takayoshi; Son, You Lee; Tobari, Yasuko; Tsutsui, Kazuyoshi

Frontiers in Endocrinology3(NOV)(article148)2012年12月-2012年12月 

DOIScopus

詳細

概要:Gonadotropin-inhibitory hormone (GnIH) was first identified in the Japanese quail as a hypothalamic neuropeptide inhibitor of gonadotropin secretion. Subsequent studies have shown that GnIH is present in the brains of birds including songbirds, and mammals including humans. The identified avian and mammalian GnIH peptides universally possess an LPXRFamide (X = L or Q) motif at their C-termini. Mammalian GnIH peptides are also designated as RFamide-related peptides from their structures. The receptor for GnIH is the G protein-coupled receptor 147 (GPR147), which is thought to be coupled to Gαi protein. Cell bodies of GnIH neurons are located in the paraventricular nucleus (PVN) in birds and the dorsomedial hypothalamic area (DMH) in mammals. GnIH neurons in the PVN or DMH project to the median eminence to control anterior pituitary function. GPR147 is expressed in the gonadotropes and GnIH suppresses synthesis and release of gonadotropins. It was further shown in immortalized mouse gonadotrope cell line (LβT2 cells) that GnIH inhibits gonadotropin-releasing hormone (GnRH) induced gonadotropin subunit gene transcriptions by inhibiting adenylate cyclase/cAMP/PKA-dependent ERK pathway. GnIH neurons also project to GnRH neurons in the preoptic area, and GnRH neurons express GPR147 in birds and mammals. Accordingly, GnIH may inhibit gonadotropin synthesis and release by decreasing the activity of GnRH neurons as well as directly acting on the gonadotropes. GnIH also inhibits reproductive behavior possibly by acting within the brain. GnIH expression is regulated by a nocturnal hormone melatonin and stress in birds and mammals. Accordingly, GnIH may play a role in translating environmental information to inhibit reproductive physiology and behavior of birds and mammals. Finally, GnIH has therapeutic potential in the treatment of reproductive cycle and hormone-dependent diseases, such as precocious puberty, endometriosis, uterine fibroids, and prostatic and breast cancers. © 2012 Ubuka, Son, Tobari and Tsutsui.

Review: Control of circadian activity of birds by the interaction of melatonin with 7α-hydroxypregnenolone, a newly discovered neurosteroid stimulating locomotion

Tsutsui, Kazuyoshi; Haraguchi, Shogo; Inoue, Kazuhiko; Miyabara, Hitomi; Suzuki, Saori; Ubuka, Takayoshi

Journal of Ornithology153(SUPPL. 1)p.235 - 2432012年08月-2012年08月 

DOIScopus

詳細

ISSN:00218375

概要:Melatonin regulates diurnal locomotor rhythms in birds as well as in other vertebrates, but the molecular mechanism by which melatonin regulates locomotor activity is poorly understood. Here, we summarize new findings showing that 7α-hydroxypregnenolone, a previously undescribed avian neurosteroid, mediates melatonin action on diurnal locomotor rhythms in birds. Recently, 7α-hydroxypregnenolone was identified as a novel avian neurosteroid in Japanese quail Coturnix japonica brain. It was found that 7α-hydroxypregnenolone acutely stimulates quail locomotor activity. Subsequently, it was clarified that diurnal changes in 7α-hydroxypregnenolone synthesis occur in parallel with changes in locomotor activity in quail. Finally, it was demonstrated that melatonin depresses the synthesis of 7α-hydroxypregnenolone, thus providing a mechanism through which the nocturnal increase in melatonin regulates diurnal changes in locomotor activity. This review highlights a novel molecular mechanism controlling circadian activity of birds by the interaction of melatonin with 7α-hydroxypregnenolone, a newly discovered neurosteroid stimulating locomotion. © 2011 Dt. Ornithologen-Gesellschaft e.V.

Review: Gonadotropin-inhibitory hormone (GnIH): Discovery, progress and prospect

Tsutsui, Kazuyoshi; Ubuka, Takayoshi; Bentley, George E.; Kriegsfeld, Lance J.

General and Comparative Endocrinology177(3)p.305 - 3142012年07月-2012年07月 

PubMedDOIScopus

詳細

ISSN:00166480

概要:A hypothalamic neuropeptide, gonadotropin-releasing hormone (GnRH), is the primary factor regulating gonadotropin secretion. An inhibitory hypothalamic neuropeptide for gonadotropin secretion was, until recently, unknown, although gonadal sex steroids and inhibin can modulate gonadotropin secretion. Findings from the last decade, however, indicate that GnRH is not the sole hypothalamic regulatory neuropeptide of vertebrate reproduction, with gonadotropin-inhibitory hormone (GnIH) playing a key role in the inhibition of reproduction. GnIH was originally identified in birds and subsequently in mammals and other vertebrates. GnIH acts on the pituitary and on GnRH neurons in the hypothalamus via a novel G protein-coupled receptor (GPR147). GnIH decreases gonadotropin synthesis and release, inhibiting gonadal development and maintenance. Such a down-regulation of the hypothalamo-pituitary-gonadal (HPG) axis may be conserved across vertebrates. Recent evidence further indicates that GnIH operates at the level of the gonads as an autocrine/paracrine regulator of steroidogenesis and gametogenesis. More recent evidence suggests that GnIH also acts both upstream of the GnRH system and at the level of the gonads to appropriately regulate reproductive activity across the seasons and during times of stress. The discovery of GnIH has fundamentally changed our understanding of hypothalamic control of reproduction. This review summarizes the discovery, progress and prospect of GnIH, a key regulator of vertebrate reproduction. © 2012 Elsevier Inc.

Effects of lamprey PQRFamide peptides on brain gonadotropin-releasing hormone concentrations and pituitary gonadotropin-β mRNA expression

Daukss, Dana; Gazda, Kristen; Kosugi, Takayoshi; Osugi, Tomohiro; Tsutsui, Kazuyoshi; Sower, Stacia A.

General and Comparative Endocrinology177(2)p.215 - 2192012年06月-2012年06月 

PubMedDOIScopus

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ISSN:00166480

概要:Within the RFamide peptide family, PQRFamide peptides that include neuropeptide FF and AF possess a C-terminal Pro-Gln-Arg-Phe-NH 2 motif. We previously identified PQRFamide peptides, lamprey PQRFa, PQRFa-related peptide (RP)-1 and -RP-2 by immunoaffinity purification in the brain of lamprey, one of the most ancient vertebrate species [13]. Lamprey PQRFamide peptide precursor mRNA was expressed in regions predicted to be involved in neuroendocrine regulation in the hypothalamus. However, the putative function(s) of lamprey PQRFamide peptides (PQRFa, PQRFa-RP-1 and PQRFa-RP-2) were not examined nor was the distribution of PQRFamide peptides examined in other tissues besides the brain. The objective of this study was to determine tissue distribution of lamprey PQRFamide peptide precursor mRNA, and to examine the effects of PQRFamide peptides on brain gonadotropin-releasing hormone (GnRH)-I, -II, and -III protein concentrations, and pituitary gonadotropin (GTH)-β mRNA expression in adult lampreys. Lamprey PQRFamide peptide precursor mRNA was expressed in the eye and the brain. Lamprey PQRFa at 100μg/kg increased brain concentrations of lamprey GnRH-II compared with controls. PQRFa, PQRFa-RP-1 and PQRFa-RP-2 did not significantly change brain protein concentrations of either lamprey GnRH-I, -III, or lamprey GTH-β mRNA expression in the pituitary. These data suggest that one of the PQRFamide peptides may act as a neuroregulator of at least the lamprey GnRH-II system in adult female lamprey. © 2012 Elsevier Inc.

Estradiol promotes Purkinje dendritic growth, spinogenesis, and synaptogenesis during neonatal life by inducing the expression of BDNF

Haraguchi, Shogo; Sasahara, Katsunori; Shikimi, Hanako; Honda, Shin Ichiro; Harada, Nobuhiro; Tsutsui, Kazuyoshi

Cerebellum11(2)p.416 - 4172012年06月-2012年06月 

PubMedDOIScopus

詳細

ISSN:14734222

概要:Neurosteroids are synthesized de novo from cholesterol in the brain. In rodents, the Purkinje cell actively produces several kinds of neurosteroids including estradiol during neonatal life, when cerebellar neuronal circuit formation occurs. Estradiol may be involved in cerebellar neuronal circuit formation through promoting neuronal growth and synaptic contact, because the Purkinje cell expresses estrogen receptor-β. To test this hypothesis, in this study we examined the effect of estradiol on dendritic growth, spinogenesis, and synaptogenesis in the Purkinje cell using neonatal wild-type (WT) mice or cytochrome P450 aromatase knock-out (ArKO) mice. Administration of estradiol to neonatal WT or ArKO mice increased dendritic growth, spinogenesis, and synaptogenesis in the Purkinje cell. In contrast, WT mice treated with tamoxifen, an ER antagonist, or ArKO mice exhibited decreased Purkinje dendritic growth, spinogenesis, and synaptogenesis at the same neonatal period. Estrogen administration to neonatal WT or ArKO mice increased the expression of brain-derived neurotrophic factor (BDNF) in the cerebellum, whereas tamoxifen decreased the BDNF level in WT mice similar to ArKO mice. BDNF administration to tamoxifentreated WT mice increased Purkinje dendritic growth. These results indicate that estradiol induces dendritic growth, spinogenesis, and synaptogenesis in the developing Purkinje cell via BDNF action during neonatal life. ©Springer Science+Business Media, LLC 2011.

Neurosteroid biosynthesis and action during cerebellar development

Tsutsui, Kazuyoshi

Cerebellum11(2)p.414 - 4152012年06月-2012年06月 

PubMedDOIScopus

詳細

ISSN:14734222

概要:The formation of the mammalian cerebellar cortex becomes complete in the neonate through the processes of migration of external granule cells, neuronal and glial growth, and synaptogenesis. In the middle 1990s, we identified the Purkinje cell, a principal cerebellar neuron, as a major site for neurosteroid formation in mammals. This discovery has provided the opportunity to understand neuronal neurosteroidogenesis and neurosteroid actions on neuronal growth and synaptic formation in the cerebellum. Based on extensive studies on mammals over the past decade, we now know that the Purkinje cell actively synthesizes progesterone and estradiol de novo from cholesterol during neonatal life, when cerebellar neuronal circuit formation occurs. Both progesterone and estradiol promote dendritic growth, spinogenesis, and synaptogenesis via each cognate nuclear receptor in the developing Purkinje cell. Such neurosteroid actions that may be mediated by neurotrophic factors contribute to the formation of cerebellar neuronal circuit during neonatal life. Allopregnanolone, a progesterone metabolite, is also synthesized in the cerebellum and acts on Purkinje cell survival in the neonate. This paper highlights the biosynthesis and biological actions of neurosteroids in the Purkinje cell during cerebellar development. ©Springer Science+Business Media, LLC 2011.

7α-Hydroxypregnenolone, a new key regulator of amphibian locomotion: Discovery, progress and prospect

Tsutsui, Kazuyoshi; Haraguchi, Shogo; Matsunaga, Masahiro; Koyama, Teppei; Do Rego, Jean Luc; Vaudry, Hubert

General and Comparative Endocrinology176(3)p.440 - 4472012年05月-2012年05月 

PubMedDOIScopus

詳細

ISSN:00166480

概要:Seasonally-breeding amphibians have served as excellent animal models to investigate the biosynthesis and biological actions of neurosteroids. Previous studies have demonstrated that the brain of amphibians possesses key steroidogenic enzymes and produces pregnenolone, a precursor of steroid hormones, and other various neurosteroids. We recently found that the brain of seasonally-breeding newts actively produces 7α-hydroxypregnenolone, a previously undescribed amphibian neurosteroid. This novel amphibian neurosteroid acts as a neuronal modulator to stimulate locomotor activity in newts. Subsequently, the mode of action of 7α-hydroxypregnenolone has been demonstrated in the newt brain. 7α-Hydroxypregnenolone stimulates locomotor activity through activation of the dopaminergic system. To understand the functional significance of 7α-hydroxypregnenolone in the regulation of locomotor activity, diurnal and seasonal changes in synthesis of 7α-hydroxypregnenolone have also been demonstrated in the newt brain. Melatonin derived from the pineal gland and eyes regulates 7α-hydroxypregnenolone synthesis in the brain, thus inducing diurnal locomotor changes. Prolactin, an adenohypophyseal hormone, regulates 7α-hydroxypregnenolone synthesis in the brain, and also induces seasonal locomotor changes. In addition, 7α-hydroxypregnenolone mediates corticosterone action to increase locomotor activity under stress. This review summarizes the discovery, progress and prospect of 7α-hydroxypregnenolone, a new key regulator of amphibian locomotion. © 2011 Elsevier Inc.

Gonadotropin-inhibitory hormone inhibits gnrh-induced gonadotropin subunit gene transcriptions by inhibiting AC/cAMP/PKA-dependent ERK pathway in LβT2 Cells

Son, You Lee; Ubuka, Takayoshi; Millar, Robert P.; Kanasaki, Haruhiko; Tsutsui, Kazuyoshi

Endocrinology153(5)p.2332 - 23432012年05月-2012年05月 

PubMedDOIScopus

詳細

ISSN:00137227

概要:A neuropeptide that directly inhibits gonadotropin secretion from the pituitary was discovered in quail and named gonadotropin-inhibitory hormone (GnIH). The presence and functional roles of GnIH orthologs, RF-amide-related peptides (RFRP), that possess a common C-terminal LPXRF-amide (X = LorQ) motif have also been demonstrated in mammals. GnIH orthologs inhibit gonadotropin synthesis and release by acting on pituitary gonadotropes and GnRH neurons in the hypothalamus via its receptor (GnIH receptor). It is becoming increasingly clear that GnIH is an important hypothalamic neuropeptide controlling reproduction, but the detailed signaling pathway mediating the inhibitory effect of GnIH on target cells is still unknown. In the present study, we investigated the pathway of GnIH cell signaling and its possible interaction with GnRH signaling using a mouse gonadotropecell line, LβT2. First, we demonstrated the expression of GnIH receptor mRNA in LβT2 cells by RT-PCR. We then examined the inhibitory effects of mouse GnIH orthologs [mouse RFRP (mRFRP)] on GnRH-induced cell signaling events. We showed that mRFRP effectively inhibited GnRH-induced cAMP signaling by using a cAMP-sensitive reporter system and measuring cAMP levels, indicating that mRFRP function as an inhibitor of adenylate cyclase. We further showed that mRFRP inhibited GnRH-stimulated ERK phosphorylation, and this effect was mediated by the inhibition of the protein kinase A pathway. Finally, we demonstrated that mRFRP inhibited GnRHstimulated gonadotropin subunit gene transcriptions and also LH release. Taken together, the results indicate that mRFRP function as GnIH to inhibit GnRH-induced gonadotropin subunit gene transcriptions by inhibiting adenylate cyclase/cAMP/protein kinase A-dependent ERK activation in LβT2 cells. © 2012 by The Endocrine Society.

Evolutionary origin of the structure and function of gonadotropin- inhibitory hormone: Insights from lampreys

Osugi, Tomohiro; Daukss, Dana; Gazda, Kristen; Ubuka, Takayoshi; Kosugi, Takayoshi; Nozaki, Masumi; Sower, Stacia A.; Tsutsui, Kazuyoshi

Endocrinology153(5)p.2362 - 23742012年05月-2012年05月 

PubMedDOIScopus

詳細

ISSN:00137227

概要:Gonadotropin (GTH)-inhibitory hormone (Gn IH) is a novel hypothalamic neuropeptide that inhibits GTH secretion in mammals and birds by acting on gonadotropes and Gn RH neurons within the hypothalamic-pituitary-gonadal axis. Gn IH and its orthologs that have an LPXRFamide (X = L orQ) motif at the Cterminus (LPXRFamide peptides) have been identified in representative species of gnathostomes. However, the identity of an LPXRFamide peptide had yet to be identified in agnathans, the most ancient lineage of vertebrates, leaving open the question of the evolutionary origin of Gn IH and its ancestral function(s). In this study, we identified an LPXRFamide peptide gene encoding three peptides (LPXRFa-1a, LPXRFa-1b, and LPXRFa-2) from the brain of sea lamprey by synteny analysis and cDNA cloning, and the mature peptides by immunoaffinity purification and mass spectrometry. The expression of lamprey LPXRFamide peptide precursor mRNA was localized in the brain and gonad by RT-PCR and in the hypothalamus by in situ hybridization. Immunohistochemistry showed appositions of lamprey LPXRFamide peptide immunoreactive fibers in close proximity to Gn RH-III neurons, suggesting that lamprey LPXRFamide peptides act on Gn RH-III neurons. In addition, lamprey LPXRFa-2 stimulated the expression of lamprey Gn RH-III protein in the hypothalamus and GTHβ mRNA expression in the pituitary. Synteny and phylogenetic analyses suggest that the LPXRFamide peptide gene diverged from a common ancestral gene likely through gene duplication in the basal vertebrates. These results suggest that one ancestral function of LPXRFamide peptides may be stimulatory compared with the inhibitory function seen in laterevolved vertebrates (birds and mammals). © 2012 by The Endocrine Society.

Acute stress increases the synthesis of 7α-hydroxypregnenolone, a new key neurosteroid stimulating locomotor activity, through corticosterone action in newts

Haraguchi, Shogo; Koyama, Teppei; Hasunuma, Itaru; Okuyama, Shin Ichiro; Ubuka, Takayoshi; Kikuyama, Sakae; Do Rego, Jean Luc; Vaudry, Hubert; Tsutsui, Kazuyoshi

Endocrinology153(2)p.794 - 8052012年02月-2012年02月 

PubMedDOIScopus

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ISSN:00137227

概要:7α-Hydroxypregnenolone (7α-OH PREG) is a newly identified bioactive neurosteroid stimulating locomotor activity in the brain of newt, a wild animal, which serves as an excellent model to investigate the biosynthesis and biological action of neurosteroids. Here,weshow that acute stress increases 7α-OH PREG synthesis in the dorsomedial hypothalamus (DMH) through corticosterone (CORT) action in newts. A 30-min restraint stress increased 7α-OH PREG synthesis in the brain tissue concomitant with the increase in plasma CORT concentrations. A 30-min restraint stress also increased the expression of cytochrome P450 7α (CYP7B), the steroidogenic enzyme of 7α-OH PREG formation, in the DMH. Decreasing plasma CORT concentrations by hypophysectomy or trilostane administration decreased 7α-OH PREG synthesis in the diencephalon, whereas administration of CORT to these animals increased 7α-OH PREG synthesis. Glucocorticoid receptor was present in DMH neurons expressing CYP7B. Thus, CORT appears to act directly on DMH neurons to increase 7α-OH PREG synthesis. We further investigated the biological action of 7α-OH PREG in the brain under stress. A 30-min restraint stress or central administration of 7α-OH PREG increased serotonin concentrations in the diencephalon. Double immunolabeling further showed colocalization of CYP7B and serotonin in the DMH. These results indicate that acute stress increases the synthesis of 7α-OH PREG via CORT action in the DMH, and 7α-OH PREG activates serotonergic neurons in the DMH that may coordinate behavioral responses to stress. This is the first demonstration of neurosteroid biosynthesis regulated by peripheral steroid hormone and of neurosteroid action in the brain under stress in any vertebrate class. Copyright © 2012 by The Endocrine Society.

Resveratrol promotes expression of SIRT1 and StAR in rat ovarian granulosa cells: An implicative role of SIRT1 in the ovary

Morita, Yoshihiro; Wada-Hiraike, Osamu; Yano, Tetsu; Shirane, Akira; Hirano, Mana; Hiraike, Haruko; Koyama, Satoshi; Oishi, Hajime; Yoshino, Osamu; Miyamoto, Yuichiro; Sone, Kenbun; Oda, Katsutoshi; Nakagawa, Shunsuke; Tsutsui, Kazuyoshi; Taketani, Yuji

Reproductive Biology and Endocrinology10p.14 - 242012年02月-2012年02月 

PubMedDOIScopus

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概要:Background: Resveratrol is a natural polyphenolic compound known for its beneficial effects on energy homeostasis, and it also has multiple properties, including anti-oxidant, anti-inflammatory, and anti-tumor activities. Recently, silent information regulator genes (Sirtuins) have been identified as targets of resveratrol. Sirtuin 1 (SIRT1), originally found as an NAD +-dependent histone deacetylase, is a principal modulator of pathways downstream of calorie restriction, and the activation of SIRT1 ameliorates glucose homeostasis and insulin sensitivity. To date, the presence and physiological role of SIRT1 in the ovary are not known. Here we found that SIRT1 was localized in granulosa cells of the human ovary.Methods: The physiological roles of resveratrol and SIRT1 in the ovary were analyzed. Immunohistochemistry was performed to localize the SIRT1 expression. SIRT1 protein expression of cultured cells and luteinized human granulosa cells was investigated by Western blot. Rat granulosa cells were obtained from diethylstilbestrol treated rats. The cells were treated with increasing doses of resveratrol, and subsequently harvested to determine mRNA levels and protein levels. Cell viability was tested by MTS assay. Cellular apoptosis was analyzed by caspase 3/7 activity test and Hoechst 33342 staining.Results: SIRT1 protein was expressed in the human ovarian tissues and human luteinized granulosa cells. We demonstrated that resveratrol exhibited a potent concentration-dependent inhibition of rat granulosa cells viability. However, resveratrol-induced inhibition of rat granulosa cells viability is independent of apoptosis signal. Resveratrol increased mRNA levels of SIRT1, LH receptor, StAR, and P450 aromatase, while mRNA levels of FSH receptor remained unchanged. Western blot analysis was consistent with the results of quantitative real-time RT-PCR assay. In addition, progesterone secretion was induced by the treatment of resveratrol.Conclusions: These results suggest a novel mechanism that resveratrol could enhance progesterone secretion and expression of luteinization-related genes in the ovary, and thus provide important implications to understand the mechanism of luteal phase deficiency. © 2012 Morita et al; licensee BioMed Central Ltd.

Identification, expression, and physiological functions of Siberian hamster gonadotropin-inhibitory hormone

Ubuka, Takayoshi; Inoue, Kazuhiko; Fukuda, Yujiro; Mizuno, Takanobu; Ukena, Kazuyoshi; Kriegsfeld, Lance J.; Tsutsui, Kazuyoshi

Endocrinology153(1)p.373 - 3852012年01月-2012年01月 

PubMedDOIScopus

詳細

ISSN:00137227

概要:Gonadotropin-inhibitory hormone (GnIH) is a hypothalamic neuropeptide that inhibits gonadotropin secretion in birds and mammals. To further understand its physiological roles in mammalian reproduction, we identified its precursor cDNA and endogenous mature peptides in the Siberian hamster brain. The Siberian hamster GnIH precursor cDNA encoded two RFamide-related peptide (RFRP) sequences. SPAPANKVPHSAANLPLRF-NH 2 (Siberian hamster RFRP-1) and TLSRVPSLPQRFNH 2 (Siberian hamster RFRP-3) were confirmed as mature endogenous peptides by mass spectrometry from brain samples purified by immunoaffinity chromatography. GnIH mRNA expression was higher in long days (LD) compared with short days (SD). GnIH mRNA was also highly expressed in SD plus pinealectomized animals, whereas expression was suppressed by melatonin, a nocturnal pineal hormone, administration. GnIH-immunoreactive (-ir) neurons were localized to the dorsomedial region of the hypothalamus, and GnIH-ir fibers projected to hypothalamic and limbic structures. The density of GnIH-ir perikarya and fibers were higher in LD and SD plus pinealectomized hamsters than in LD plus melatonin or SD animals. The percentage of GnRH neurons receiving close appositions from GnIH-ir fiber terminals was also higher in LD than SD, and GnIH receptor was expressed in GnRH-ir neurons. Finally, central administration of hamster RFRP-1 or RFRP-3 inhibited LH release 5 and 30 min after administration in LD. In sharp contrast, both peptides stimulated LH release 30 min after administration in SD. These results suggest that GnIH peptides fine tune LH levels via its receptor expressed in GnRH-ir neurons in an opposing fashion across the seasons in Siberian hamsters. Copyright © 2012 by The Endocrine Society.

Localization of gonadotropin-releasing hormone (GnRH), gonadotropin-inhibitory hormone (GnIH), kisspeptin and GnRH receptor and their possible roles in testicular activities from birth to senescence in mice.

S. Anjum, A. Krishna, R. Sridaran and K. Tsutsui

J. Exp. Zool. Part A317p.630 - 6442012年-

DOI

Involvement of a neurosteroid, 7α-hydroxypregnenolone in the courtship behavior performed by the male newt, Cynops pyrrhogaster.

F. Toyoda, I. Hasunuma, T. Nakada, S. Haraguchi, K. Tsutsui and S. Kikuyama

Horm. Behav.62p.375 - 3802012年-

Disrupted organization of RFamide pathways in the hypothalamus is associated with advanced puberty in female rats neonatally exposed to Bisphenol A.

S. M. Losa-Ward, K. L. Todd, K. A. McCaffrey, K. Tsutsui and H. B. Patisaul

Biol. Reprod.87p.1 - 92012年-

DOI

The human gonadotropin-inhibitory hormone ortholog RFamide-related peptide-3 suppresses gonadotropin-induced progesterone production in human granulosa cells.

H. Oishi, C. Klausen, G. E. Bentley, T. Osugi, K. Tsutsui, C. B. Gilks, T. Yano and P. C. K. Leung

Endocrinology153p.3435 - 34452012年-

Create new research directions in comparative endocrinology from Asia and Oceania.

K. Tsutsui

Gen. Comp. Endocrinol.181p.192 - 1962012年-

総説:生殖を制御する新規脳ホルモンの作用機構と発現制御機構

筒井和義

Current Topics 「New Insights of Molecular Genetics on Growth Disorders」7p.13 - 132012年-

総説:生殖を制御する新規脳ホルモンGnIHの起源と分子進化 比較内分泌学

筒井和義・大杉知裕・戸張靖子・孫 ユリ・産賀崇由

比較内分泌学38p.76 - 832012年-

Regulation of neurosteroid biosynthesis by neurotransmitters and neuropeptides.

J. L. Do Rego, J. Y. Seong, D. Burel, J. Leprince, D. Vaudry, V. Luu-The, M.-C. Tonon, K. Tsutsui, G. Pelletier and H. Vaudry

Front. Endocrin.3(4)p.1 - 152012年-

「ニューロペプチドupdate」生殖腺刺激ホルモン放出抑制ホルモン

筒井和義

Crinical Neuroscience 中外医学社30(2)p.223 - 2252012年-

Biological activity of novel lamprey RFamide peptides, specifically PQRFamide and their related peptides.

D. Daukss, K. Gazda, T. Kosugi, T. Osugi, K. Tsutsui and S. A. Sower

Gen. Comp. Endocrinol.177p.215 - 2192012年-

Hypothalamic gonadotropin-inhibitory hormone precursor mRNA is increased during depressed food intake in heat-exposed chicks.

V. S. Chowdhury, S. Tomonaga, S. Nishimura, S. Tabata, J. F. Cockrem, K. Tsutsui and M. Furuse

Comp. Biol. Physiol.162p.227 - 2332012年-

RNA interference of gonadotropin-inhibitory hormone gene induces arousal in songbirds.

T. Ubuka, M. Mukai, J. Wolfe, R. Beverly, S. Clegg, A. Wang, S. Hsia, M. Li, J. S. Krause, T. Mizuno, Y. Fukuda, K. Tsutsui, G. E. Bentley and J. C. Wingfield

PLoS ONE7p.e302022012年-

RNA Interference of Gonadotropin-Inhibitory Hormone Gene Induces Arousal in Songbirds

Ubuka, Takayoshi;Mukai, Motoko;Wolfe, Jordan;Beverly, Ryan;Clegg, Sarah;Wang, Ariel;Hsia, Serena;Li, Molly;Krause, Jesse S.;Mizuno, Takanobu;Fukuda, Yujiro;Tsutsui, Kazuyoshi;Bentley, George E.;Wingfield, John C.

PLOS ONE7(1)p.e302022012年-2012年

DOIWoS

詳細

ISSN:1932-6203

Developmental changes in the mammalian gonadotropin-inhibitory hormone (GnIH) ortholog RFamide-related peptide (RFRP) and its cognate receptor GPR147 in the rat hypothalamus

Iwasa, Takeshi;Matsuzaki, Toshiya;Murakami, Masahiro;Kinouchi, Riyo;Osugi, Tomohiro;Gereltsetseg, Ganbat;Yoshida, Shinobu;Irahara, Minoru;Tsutsui, Kazuyoshi

INTERNATIONAL JOURNAL OF DEVELOPMENTAL NEUROSCIENCE30(1)p.31 - 372012年-2012年

DOIWoS

詳細

ISSN:0736-5748

Mollusc gonadotropin-releasing hormone directly regulates gonadal functions: A primitive endocrine system controlling reproduction

Treen, Nicholas;Itoh, Naoki;Miura, Hanae;Kikuchi, Ippei;Ueda, Takenori;Takahashi, Keisuke G.;Ubuka, Takayoshi;Yamamoto, Kazutoshi;Sharp, Peter J.;Tsutsui, Kazuyoshi;Osada, Makoto

GENERAL AND COMPARATIVE ENDOCRINOLOGY176(2)p.167 - 1722012年-2012年

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ISSN:0016-6480

Evolutionary Origin of Gonadotropin-Inhibitory Hormone (GnIH): Isolation, localization and Biological Activity of Lamprey GnIH Ortholog

Sower, Stacia;Osugi, Tomohiro;Daukss, Dana;Gazda, Kristen;Ubuka, Takayoshi;Kosugi, Takayoshi;Tsutsui, Kazuyoshi

INTEGRATIVE AND COMPARATIVE BIOLOGY52p.E165 - E1652012年-2012年

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ISSN:1540-7063

7α-Hydroxypregnenolone, a new key regulator of amphibian locomotion: Discovery, progress and prospect

Tsutsui, Kazuyoshi;Haraguchi, Shogo;Matsunaga, Masahiro;Koyama, Teppei;Do Rego, Jean-Luc;Vaudry, Hubert

GENERAL AND COMPARATIVE ENDOCRINOLOGY176(3)p.440 - 4472012年-2012年

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ISSN:0016-6480

Gonadotropin-Inhibitory Hormone Inhibits GnRH-Induced Gonadotropin Subunit Gene Transcriptions by Inhibiting AC/cAMP/PKA-Dependent ERK Pathway in L beta T2 Cells

Son, You Lee;Ubuka, Takayoshi;Millar, Robert P.;Kanasaki, Haruhiko;Tsutsui, Kazuyoshi

ENDOCRINOLOGY153(5)p.2332 - 23432012年-2012年

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ISSN:0013-7227

Evolutionary Origin of the Structure and Function of Gonadotropin-Inhibitory Hormone: Insights from Lampreys

Osugi, Tomohiro;Daukss, Dana;Gazda, Kristen;Ubuka, Takayoshi;Kosugi, Takayoshi;Nozaki, Masumi;Sower, Stacia A.;Tsutsui, Kazuyoshi

ENDOCRINOLOGY153(5)p.2362 - 23742012年-2012年

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ISSN:0013-7227

Estradiol Promotes Purkinje Dendritic Growth, Spinogenesis, and Synaptogenesis During Neonatal Life by Inducing the Expression of BDNF

Haraguchi, Shogo;Sasahara, Katsunori;Shikimi, Hanako;Honda, Shin-ichiro;Harada, Nobuhiro;Tsutsui, Kazuyoshi

CEREBELLUM11(2)p.416 - 4172012年-2012年

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ISSN:1473-4222

Hypothalamic gonadotropin-inhibitory hormone precursor mRNA is increased during depressed food intake in heat-exposed chicks

Chowdhury, Vishwajit S.;Tomonaga, Shozo;Nishimura, Shotaro;Tabata, Shoji;Cockrem, John F.;Tsutsui, Kazuyoshi;Furuse, Mitsuhiro

COMPARATIVE BIOCHEMISTRY AND PHYSIOLOGY A-MOLECULAR & INTEGRATIVE PHYSIOLOGY162(3)p.227 - 2332012年-2012年

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ISSN:1095-6433

Effects of lamprey PQRFamide peptides on brain gonadotropin-releasing hormone concentrations and pituitary gonadotropin-beta mRNA expression

Daukss, Dana;Gazda, Kristen;Kosugi, Takayoshi;Osugi, Tomohiro;Tsutsui, Kazuyoshi;Sower, Stacia A.

GENERAL AND COMPARATIVE ENDOCRINOLOGY177(2)p.215 - 2192012年-2012年

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ISSN:0016-6480

The Human Gonadotropin-Inhibitory Hormone Ortholog RFamide-Related Peptide-3 Suppresses Gonadotropin-Induced Progesterone Production in Human Granulosa Cells

Oishi, Hajime;Klausen, Christian;Bentley, George E.;Osugi, Tomohiro;Tsutsui, Kazuyoshi;Gilks, C. Blake;Yano, Tetsu;Leung, Peter C. K.

ENDOCRINOLOGY153(7)p.3435 - 34452012年-2012年

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ISSN:0013-7227

Control of circadian activity of birds by the interaction of melatonin with 7 alpha-hydroxypregnenolone, a newly discovered neurosteroid stimulating locomotion

Tsutsui, Kazuyoshi;Haraguchi, Shogo;Inoue, Kazuhiko;Miyabara, Hitomi;Suzuki, Saori;Ubuka, Takayoshi

JOURNAL OF ORNITHOLOGY153p.S235 - S2432012年-2012年

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ISSN:0021-8375

Involvement of the neurosteroid 7 alpha-hydroxypregnenolone in the courtship behavior of the male newt Cynops pyrrhogaster

Toyoda, Fumiyo;Hasunuma, Itaru;Nakada, Tomoaki;Haraguchi, Shogo;Tsutsui, Kazuyoshi;Kikuyama, Sakae

HORMONES AND BEHAVIOR62(4)p.375 - 3802012年-2012年

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ISSN:0018-506X

Localization of Gonadotropin-Releasing Hormone (GnRH), Gonadotropin-Inhibitory Hormone (GnIH), Kisspeptin and GnRH Receptor and Their Possible Roles in Testicular Activities From Birth to Senescence in Mice

Anjum, Shabana;Krishna, Amitabh;Sridaran, Rajagopala;Tsutsui, Kazuyoshi

JOURNAL OF EXPERIMENTAL ZOOLOGY PART A-ECOLOGICAL GENETICS AND PHYSIOLOGY317A(10)p.630 - 6442012年-2012年

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ISSN:1932-5223

生殖を制御する新規脳ホルモンGnIHの起源と分子進化

筒井 和義;大杉 知裕;戸張 靖子;孫 ユリ;産賀 崇由

比較内分泌学38(145)p.76 - 832012年-2012年

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ISSN:1882-6636

The 10th International Symposium on Avian Endocrinology 2012(ISAE2012 Gifu)主催記

筒井 和義;吉村 崇

比較内分泌学38(146)p.174 - 1772012年-2012年

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ISSN:1882-6636

Possible role of pineal allopregnanolone in Purkinje cell survival

Haraguchi, Shogo;Hara, Sakurako;Ubuka, Takayoshi;Mita, Masatoshi;Tsutsui, Kazuyoshi

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA109(51)p.21110 - 211152012年-2012年

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ISSN:0027-8424

Disrupted Organization of RFamide Pathways in the Hypothalamus Is Associated with Advanced Puberty in Female Rats Neonatally Exposed to Bisphenol A

Losa-Ward, Sandra M.;Todd, Karina L.;McCaffrey, Katherine A.;Tsutsui, Kazuyoshi;Patisaul, Heather B.

BIOLOGY OF REPRODUCTION87(2)p.1 - 92012年-2012年

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ISSN:0006-3363

Editorial: Research Topic on Neurosteroids

H. Vaudry and K. Tsutsui

Front. Endocrinol.3(article 126)2012年-

DOI

Developmental changes in the mammalian gonadotropin-inhibitory hormone (GnIH) ortholog RFamide-related peptide (RFRP) and its cognate receptor GPR147 in the rat hypothalamus

T. Iwasa, T. Matsuzaki, M. Murakami, R. Kinouchi, T. Osugi, G. Gereltsetseg, S. Yoshida, A. Kuwahara, T. Yasui, M. Irahara and K. Tsutsui

Int. J. Dev. Neurosci.30p.31 - 372012年-2012年

Biosynthesis, mode of action, and functional significance of neurosteroids in the Purkinje cell

Tsutsui, Kazuyoshi; Ukena, Kazuyoshi; Sakamoto, Hirotaka; Okuyama, Shin Ichiro; Haraguchi, Shogo

Frontiers in Endocrinology2(OCT)(article61)p.1 - 92011年12月-2011年12月 

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概要:The brain has traditionally been considered to be a target site of peripheral steroid hormones. In addition to this classical concept, we now know that the brain has the capacity to synthesize steroids de novo from cholesterol, the so-called "neurosteroids." In the middle 1990s, the Purkinje cell, an important cerebellar neuron, was identified as a major site for neurosteroid formation in the brain of mammals and other vertebrates. This discovery has provided the opportunity to understand neuronal neurosteroidogenesis in the brain. In addition, biological actions of neurosteroids are becoming clear by the studies using the Purkinje cell, an excellent cellular model, which is known to play an important role in memory and learning processes. Based on the studies on mammals over the past decade, it is considered that the Purkinje cell actively synthesizes progesterone and estradiol from cholesterol during neonatal life, when cerebellar neuronal circuit formation occurs. Both progesterone and estradiol promote dendritic growth, spinogenesis, and synaptogenesis via each cognate nuclear receptor in the developing Purkinje cell. Such neurosteroid actions mediated by neurotrophic factors may contribute to the formation of cerebellar neuronal circuit during neonatal life. 3α,5α-Tetrahydroprogesterone (allopregnanolone), a progesterone metabolite, is also synthesized in the cerebellum and considered to act as a survival factor of Purkinje cells in the neonate. This review summarizes the current knowledge regarding the biosynthesis, mode of action, and functional significance of neurosteroids in the Purkinje cell during development in terms of synaptic formation of cerebellar neuronal networks. © 2011 Tsutsui, Ukena, Sakamoto, Okuyama and Haraguchi.

Neurosteroid biosynthesis and function in the brain of domestic birds

Tsutsui, Kazuyoshi

Frontiers in Endocrinology2(37)p.1 - 142011年12月-2011年12月 

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概要:It is now established that the brain and other nervous systems have the capability of form-ing steroids de novo, the so-called "neurosteroids." The pioneering discovery of Baulieu and his colleagues, using rodents, has opened the door to a new research field of "neuros-teroids." In contrast to mammalian vertebrates, little has been known regarding de novo neurosteroidogenesis in the brain of birds. We therefore investigated neurosteroid forma-tion and metabolism in the brain of quail, a domestic bird. Our studies over the past two decades demonstrated that the quail brain possesses cytochrome P450 side-chain cleav-age enzyme (P450scc), 3β-hydroxysteroid dehydrogenase/Δ5-Δ4-isomerase (3β-HSD), 5β-reductase, cytochrome P45017α-hydroxylase/c17,20-lyase (P45017α,lyase), 17β-HSD, etc., and produces pregnenolone, progesterone, 5β-dihydroprogesterone (5β-DHP), 3β, 5β-tetrahydroprogesterone (3β,5β-THP), androstenedione, testosterone, and estradiol from cholesterol. Independently, Schlinger's laboratory demonstrated that the brain of zebra finch, a songbird, also produces various neurosteroids.Thus, the formation and metabolism of neurosteroids from cholesterol is now known to occur in the brain of birds. In addition, we recently found that the quail brain expresses cytochrome P4507α and produces 7α-and 7β-hydroxypregnenolone, previously undescribed avian neurosteroids, from pregnenolone. This paper summarizes the advances made in our understanding of neurosteroid formation and metabolism in the brain of domestic birds.This paper also describes what are currently known about physiological changes in neurosteroid formation and biological functions of neurosteroids in the brain of domestic and other birds. © 2011 Tsutsui.

Characterization of novel RFamide peptides in the central nervous system of the brown hagfish: Isolation, localization, and functional analysis

Osugi, Tomohiro; Uchida, Katsuhisa; Nozaki, Masumi; Tsutsui, Kazuyoshi

Endocrinology152(11)p.4252 - 42642011年11月-2011年11月 

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ISSN:00137227

概要:RFamide (RFa) peptides play various important roles in the central nervous system in both invertebrates and vertebrates. However, there is no evidence of the existence of any RFamide peptide in the brain of hagfish, one of the oldest lineages of vertebrates. In this study,wesought to identify novel RFamide peptides from the brains of hagfish (Paramyxine atami). We identified four novel RFamide peptides, which had the C-terminal Pro-Gln-Arg-Phe-NH 2 structure. cDNA cloning revealed that the identified RFamide peptides are encoded in two types of cDNA. Molecular phylogenetic analysis of the two precursors indicated that the hagfish RFamide peptides belong to the PQRFamide peptide group that includes mammalian neuropeptide FF and AF. Based on immunohistochemistry and in situ hybridization, hagfish PQRFamide peptide precursor mRNA and its translated peptides were localized in the infundibular nucleus of the hypothalamus. Immunoreactive fibers were terminated on blood vessels in the infundibular nucleus. Dense immunoreactive fibers were also observed in other brain regions. We further showed that one of the hagfish PQRFamide peptides significantly stimulated the expression of gonadotropin-β mRNA in the cultured hagfish pituitary. These results indicate that the control mechanism of gonadotropin expression by a hypothalamic neuropeptide evolved in the agnathan brain. This is the first evidence describing the identification of RFamide peptides in the hagfish brain. This is also the first report showing the regulation of gonadotropin expression by a homolog of neuropeptide FF that belongs to the PQRFamide peptide group in any vertebrate. Copyright © 2011 by The Endocrine Society.

Identification, localization and expression of LPXRFamide peptides, and melatonin-dependent induction of their precursor mRNA in the newt brain

Chowdhury, Vishwajit Sur; Chowdhury, Vishwajit Sur; Ubuka, Takayoshi; Osugi, Tomohiro; Shimura, Taichi; Tsutsui, Kazuyoshi

Journal of Endocrinology209(2)p.211 - 2202011年05月-2011年05月 

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ISSN:00220795

概要:The existence of RFamide peptides with a C-terminal LPXRFamide (XZL or Q) motif has been identified in the brain of various vertebrate species. However, the presence of LPXRFamide peptides in the urodele brain is not yet known. In this study, we cloned a cDNA encoding the precursor of LPXRFamide peptides from the newt brain by a combination of 3' and 5' rapid amplification of cDNA ends. The deduced LPXRFamide peptide precursor consisted of 233 amino acid residues, encoding four putative LPXRFamide peptides. All the peptide sequences were flanked by a glycine C-terminal amidation signal and basic amino acid on each end as an endoproteolytic site. Mass spectrometric analyses detected a nonapeptide, two decapeptides and an octapeptide produced from the precursor polypeptide in the brain as endogenous ligands. In situ hybridization further revealed the cellular localization of newt LPXRFamide (nLPXRFa) precursor mRNA in the suprachiasmatic nucleus (SCN) in the newt hypothalamus. Immunocytochemistry showed a cluster of cell bodies restricted to the SCN and their terminals in the median eminence. To understand the regulatory mechanism of nLPXRFa peptide expression, we further analyzed the effect of melatonin on the expression of nLPXRFa precursor mRNA. Melatonin administration to newts increased the expression of nLPXRFa precursor mRNA in the diencephalon. These results indicate that the urodele hypothalamus possesses LPXRFamide peptides and the expression of LPXRFamide peptides is regulated by melatonin. The localization of nLPXRFa peptides further suggests that these peptides may be involved in the regulation of pituitary hormone release in newts. © 2011 Society for Endocrinology.

Historical view of development of comparative endocrinology in Japan

Kikuyama, Sakae; Tsutsui, Kazuyoshi

General and Comparative Endocrinology171(2)p.117 - 1232011年04月-2011年04月 

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ISSN:00166480

概要:This article describing a brief history of development of comparative endocrinology in Japan is contributed to the journal General and Comparative Endocrinology, in commemoration of the 50th anniversary of its publication. It covers significant works in the field of comparative endocrinology that have been done by Japanese endocrinologists, focusing those achieved during the past 70. years. The contents were arranged according to the taxonomical order of the experimental animals with which individual researchers or research groups have contributed to the acquisition of important knowledge in comparative endocrinology. © 2011 Elsevier Inc.

Molecular evolution and functional characterization of the orexigenic peptide 26RFa and its receptor in vertebrates

Ukena, Kazuyoshi; Vaudry, Hubert; Leprince, Jérôme; Tsutsui, Kazuyoshi

Cell and Tissue Research343(3)p.475 - 4812011年03月-2011年03月 

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ISSN:0302766X

概要:Several neuropeptides possessing the RFamide motif at their C-termini (designated RFamide peptides) have been characterized in the hypothalamus of a variety of vertebrates. To date, five groups of the RFamide peptide family have been shown to exert several important neuroendocrine, behavioral, sensory, and autonomic functions. Since the discovery of the 26-amino acid RFamide peptide (termed 26RFa) from the frog brain, 26RFa has been shown to exert orexigenic activity in mammals and to be a ligand of the previously identified orphan G-protein-coupled receptor GPR103. Recently, 26RFa and its cognate receptor GPR103 have been identified in the brain of birds. This mini-review summarizes the advances in the identification, localization, and functions of 26RFa and its cognate receptor GPR103 in vertebrates and highlights recent progress made in birds. © 2011 Springer-Verlag.

GnIHの発見とGnIH研究の進展・展望 : 鳥類から哺乳類、ヒトへの展開

筒井 和義

比較内分泌学 = Comparative endocrinology37(140)p.21 - 282011年02月-2011年02月 

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ISSN:18826636

Expression of cytochrome P450 side-chain cleavage enzyme mRNA and production of pregnenolone in the brain of the red-bellied newt Cynops pyrrhogaster

Takase, Minoru; Haraguchi, Shogo; Hasunuma, Itaru; Kikuyama, Sakae; Tsutsui, Kazuyoshi

General and Comparative Endocrinology170(3)p.468 - 4742011年02月-2011年02月 

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ISSN:00166480

概要:It is becoming clear that the vertebrate brain has the capability of forming steroids de novo, the so-called " neurosteroids" To understand neurosteroidogenesis in the brain, it is essential to demonstrate the formation of pregnenolone, a main precursor of neurosteroids. In amphibians, the pregnenolone formation from cholesterol is still unclear, although the brain accumulates pregnenolone, pregnenolone sulfate and 7α-hydroxypregnenolone. This study was addressed to obtain basic information about pregnenolone formation in the newt brain. Firstly, we demonstrated that the newt brain produces pregnenolone from cholesterol. Subsequently, cDNA encoding cytochrome P450 side-chain cleavage enzyme (P450scc), a key steroidogenic enzyme catalyzing pregnenolone formation, was isolated from the newt. The sequence analysis showed that the isolated P450scc cDNA contained a putative coding region consisting of 1569. bp, which encoded 523 amino acids. The steroid- and heme-binding domains of P450scc were highly shared in amino acids among vertebrates. RT-PCR analysis amplified the authentic fragment corresponding to newt P450scc showed its transcription in the brain. However, the transcription level in the brain was lower than those of the gonad and the kidney including adrenals. The restricted cells in the four major regions of the newt brain, such as the telencephalon, diencephalon, mesencephalon, and rhombencephalon, were demonstrated to express P450scc transcripts by RT-PCR and in situ hybridization. Taken together, these results indicate that the newt brain expresses P450scc mRNA and produces pregnenolone from cholesterol. © 2010 Elsevier Inc.

Review: Mode of action and functional significance of 7α-hydroxypregnenolone stimulating locomotor activity.

S. Haraguchi, M. Matsunaga, H. Vaudry and K. Tsutsui

Front. Endocrin.2(23)p.1 - 82011年-

DOI

Neurosteroid biosynthesis in the brain of amphibians.

H. Vaudry, J. L. Do Rego, D. Burel, V. Luu-The, G. Pelletier and K. Tsutsui

Front. Endocrin.2(79)p.1 - 92011年-

DOI

Identification, localisation and functional implication of 26RFa orthologue peptide in the brain of zebra finch (Taeniopygia guttata).

Y. Tobari, N. Iijima, K. Tsunekawa, T. Osugi, K. Ukena, K. Okanoya, K. Tsutsui and H. Ozawa

J. Neuroendocrinol.23p.791 - 8032011年-

Synchronised expressions of LPXRFamide peptide and its receptor genes: seasonal, diurnal and circadian changes during spawning period in grass puffer.

M. Shahjahan, T. Ikegami, T. Osugi, K. Ukena, H. Doi, A. Hattori, K. Tsutsui and H. Ando

J. Neuroendocrinol.23p.39 - 512011年-

Review: GnIHによる生殖機能調節 「成長 代謝」

筒井和義

エルゼビアジャパン2p.1 - 32011年-

Estrogen biosynthesis in the gonad of the frog Rana rugosa

Isomura, Tomoko;Haraguchi, Shogo;Miyamoto, Kaoru;Tsutsui, Kazuyoshi;Nakamura, Yoriko;Nakamura, Masahisa

GENERAL AND COMPARATIVE ENDOCRINOLOGY170(1)p.207 - 2122011年-2011年

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ISSN:0016-6480

Expression of cytochrome P450 side-chain cleavage enzyme mRNA and production of pregnenolone in the brain of the red-bellied newt Cynops pyrrhogaster

Takase, Minoru;Haraguchi, Shogo;Hasunuma, Itaru;Kikuyama, Sakae;Tsutsui, Kazuyoshi

GENERAL AND COMPARATIVE ENDOCRINOLOGY170(3)p.468 - 4742011年-2011年

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ISSN:0016-6480

Effects of gonadotropin-inhibitory hormone on folliculogenesis and steroidogenesis of cyclic mice

Singh, Padmasana;Krishna, Amitabh;Tsutsui, Kazuyoshi

FERTILITY AND STERILITY95(4)p.1397 - 14042011年-2011年

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ISSN:0015-0282

Light-dependent and circadian clock-regulated activation of sterol regulatory element-binding protein, X-box-binding protein 1, and heat shock factor pathways

Hatori, Megumi;Hirota, Tsuyoshi;Iitsuka, Michiko;Kurabayashi, Nobuhiro;Haraguchi, Shogo;Kokame, Koichi;Sato, Ryuichiro;Nakai, Akira;Miyata, Toshiyuki;Tsutsui, Kazuyoshi;Fukada, Yoshitaka

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA108(12)p.4864 - 48692011年-2011年

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ISSN:0027-8424

Immunohistochemical localization of GnRH and RFamide-related peptide-3 in the ovaries of mice during the estrous cycle

Singh, Padmasana;Krishna, Amitabh;Sridaran, Rajagopala;Tsutsui, Kazuyoshi

JOURNAL OF MOLECULAR HISTOLOGY42(5)p.371 - 3812011年-2011年

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ISSN:1567-2379

Characterization of Novel RFamide Peptides in the Central Nervous System of the Brown Hagfish: Isolation, Localization, and Functional Analysis

Osugi, Tomohiro;Uchida, Katsuhisa;Nozaki, Masumi;Tsutsui, Kazuyoshi

ENDOCRINOLOGY152(11)p.4252 - 42642011年-2011年

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ISSN:0013-7227

7α-Hydroxypregnenolone, a new key regulator of locomotor activity of vertebrates: Identification, mode of action, and functional significance

Tsutsui, Kazuyoshi; Haraguchi, Shogo; Matsunaga, Masahiro; Inoue, Kazuhiko; Vaudry, Hubert

Frontiers in Endocrinology1(DEC)(article 9)p.1 - 132010年12月-2010年12月 

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概要:Steroids synthesized de novo by the central and peripheral nervous systems are called neurosteroids. The formation of neurosteroids from cholesterol in the brain was originally demonstrated in mammals by Baulieu and colleagues. Our studies over the past two decades have also shown that, in birds and amphibians as in mammals, the brain expresses several kinds of steroidogenic enzymes and produces a variety of neurosteroids. Thus, de novo neurosteroidogenesis from cholesterol is a conserved property that occurs throughout vertebrates. However, the biosynthetic pathways of neurosteroids in the brain of vertebrates was considered to be still incompletely elucidated. Recently, 7α-hydroxypregnenolone was identified as a novel bioactive neurosteroid stimulating locomotor activity in the brain of newts and quail through activation of the dopaminergic system. Subsequently, diurnal and seasonal changes in synthesis of 7α-hydroxypregnenolone in the brain were demonstrated. Interestingly, melatonin derived from the pineal gland and eyes regulates 7α-hydroxypregnenolone synthesis in the brain, thus inducing diurnal locomotor changes. Prolactin, an adenohypophyseal hormone, regulates 7α-hydroxypregnenolone synthesis in the brain, and may also induce seasonal locomotor changes. This review highlights the identification, mode of action, and functional significance of 7α-hydroxypregnenolone, a new key regulator of locomotor activity of vertebrates, in terms of diurnal and seasonal changes in 7α-hydroxypregnenolone synthesis, and describes some of their regulatory mechanisms. © 2010 Tsutsui, Haraguchi, Matsunaga, Inoue and Vaudry.

Mode of action and functional significance of 7α-hydroxypregnenolone stimulating locomotor activity

Haraguchi, Shogo; Matsunaga, Masahiro; Vaudry, Hubert; Tsutsui, Kazuyoshi

Frontiers in Endocrinology2(AUG)(article 23)p.1 - 82010年12月-2010年12月 

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概要:Previous studies over the past two decades have demonstrated that the brain and other nervous systems possess key steroidogenic enzymes and produces pregnenolone and other various neurosteroids in vertebrates in general. Recently, 7α-hydroxypregnenolone, a novel bioactive neurosteroid, was identified in the brain of newts and quail. Importantly, this novel neurosteroid is produced from pregnenolone through the enzymatic activity of cytochrome P4507α and acts on brain tissue as a neuronal modulator to stimulate locomotor activity in these vertebrates. Subsequently, the mode of action of 7α-hydroxypregnenolone was demonstrated. 7α-Hydroxypregnenolone stimulates locomotor activity through activation of the dopaminergic system. To understand the functional significance of 7α-hydroxypregnenolone in the regulation of locomotor activity, diurnal, and seasonal changes in 7α-hydroxypregnenolone synthesis were further characterized. Melatonin derived from the pineal gland and eyes regulates 7α-hydroxypregnenolone synthesis in the brain, thus inducing diurnal locomotor changes. Prolactin, an adenohypophyseal hormone, regulates 7α-hydroxypregnenolone synthesis in the brain, and also induces seasonal locomotor changes. In addition, 7α-hydroxypregnenolone mediates corticosterone action to modulate locomotor activity under stress. This review summarizes the current knowledge regarding the mode of action and functional significance of 7α-hydroxypregnenolone, a newly identified bioactive neurosteroid stimulating locomotor activity. © 2011 Haraguchi, Matsunaga, Vaudry and Tsutsui.

Review: Identification of 7α-hydroxypregnenolone, a novel bioactive amphibian neurosteroid stimulating locomotor activity, and its physiological roles in the regulation of locomotion

Tsutsui, Kazuyoshi; Haraguchi, Shogo; Matsunaga, Masahiro; Koyama, Teppei; Do Rego, Jean Luc; Vaudry, Hubert

General and Comparative Endocrinology168(2)p.275 - 2792010年09月-2010年09月 

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ISSN:00166480

概要:We now know that steroids can be synthesized de novo by the brain and the peripheral nervous system. Such steroids are called neurosteroids and de novo neurosteroidogenesis from cholesterol is a conserved property of vertebrate brains. Our studies over the past decade have demonstrated that the brain expresses several kinds of steroidogenic enzymes and produces a variety of neurosteroids in sub-mammalian species. However, neurosteroid biosynthetic pathways in amphibians, as well as other vertebrates may still not be fully mapped. We first found that the newt brain actively produces 7α-hydroxypregnenolone, a previously undescribed amphibian neurosteroid. We then demonstrated that 7α-hydroxypregnenolone acts as a novel bioactive neurosteroid to stimulate locomotor activity of newt by means of the dopaminergic system. Subsequently, we analyzed the physiological roles of 7α-hydroxypregnenolone in the regulation of locomotor activity of newt. This paper summarizes the advances made in our understanding of 7α-hydroxypregnenolone, a newly discovered bioactive amphibian neurosteroid stimulating locomotor activity, and its physiological roles in the regulation of locomotion in newt. © 2010 Elsevier Inc.

Discovery and evolutionary history of gonadotrophin-inhibitory hormone and kisspeptin: New key neuropeptides controlling reproduction

Tsutsui, K.; Bentley, G. E.; Kriegsfeld, L. J.; Osugi, T.; Seong, J. Y.; Vaudry, H.

Journal of Neuroendocrinology22(7)p.716 - 7272010年07月-2010年07月 

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詳細

ISSN:09538194

概要:Gonadotrophin-releasing hormone (GnRH) is the primary hypothalamic factor responsible for the control of gonadotrophin secretion in vertebrates. However, within the last decade, two other hypothalamic neuropeptides have been found to play key roles in the control of reproductive functions: gonadotrophin-inhibitory hormone (GnIH) and kisspeptin. In 2000, we discovered GnIH in the quail hypothalamus. GnIH inhibits gonadotrophin synthesis and release in birds through actions on GnRH neurones and gonadotrophs, mediated via GPR147. Subsequently, GnIH orthologues were identified in other vertebrate species from fish to humans. As in birds, mammalian and fish GnIH orthologues inhibit gonadotrophin release, indicating a conserved role for this neuropeptide in the control of the hypothalamic-pituitary-gonadal axis across species. Subsequent to the discovery of GnIH, kisspeptin, encoded by the KiSS-1 gene, was discovered in mammals. By contrast to GnIH, kisspeptin has a direct stimulatory effect on GnRH neurones via GPR54. GPR54 is also expressed in pituitary cells, but whether gonadotrophs are targets for kisspeptin remains unresolved. The KiSS-1 gene is also highly conserved and has been identified in mammals, amphibians and fish. We have recently found a second isoform of KiSS-1, designated KiSS-2, in several vertebrates, but not birds, rodents or primates. In this review, we highlight the discovery, mechanisms of action, and functional significance of these two chief regulators of the reproductive axis. © 2010 The Authors. Journal Compilation © 2010 Blackwell Publishing Ltd.

Gonadotropin-inhibitory hormone (GnIH) and its control of central and peripheral reproductive function

Tsutsui, Kazuyoshi; Bentley, George E.; Bedecarrats, Gregoy; Osugi, Tomohiro; Ubuka, Takayoshi; Kriegsfeld, Lance J.

Frontiers in Neuroendocrinology31(3)p.284 - 2952010年07月-2010年07月 

PubMedDOIScopus

詳細

ISSN:00913022

概要:Identification of novel neurohormones that regulate the reproductive axis is essential for the progress of neuroendocrinology. The decapeptide gonadotropin-releasing hormone (GnRH) is the primary factor responsible for the hypothalamic control of gonadotropin secretion. Gonadal sex steroids and inhibin modulate gonadotropin secretion via feedback from the gonads, but a neuropeptide that directly inhibits gonadotropin secretion was unknown in vertebrates until 2000 when a hypothalamic dodecapeptide serving this function was discovered in quail. Because of its action on cultured pituitary in quail, it was named gonadotropin-inhibitory hormone (GnIH). GnIH acts on the pituitary and on GnRH neurons in the hypothalamus via a novel G protein-coupled receptor (GPR147). GPR74 may also be a possible candidate GnIH receptor. GnIH decreases gonadotropin synthesis and release, inhibiting gonadal development and maintenance. Melatonin stimulates the expression and release of GnIH via melatonin receptors expressed by GnIH neurons. GnIH actions and interactions with GnRH seem common not only to several avian species, but also to mammals. Thus, GnIH is considered to have an evolutionarily conserved role in controlling vertebrate reproduction, and GnIH homologs have also been identified in the hypothalamus of mammals. As in birds, mammalian GnIH homologs act to inhibit gonadotropin release in several species. More recent evidence in birds and mammals indicates that GnIH may operate at the level of the gonads as an autocrine/paracrine regulator of steroidogenesis and gametogenesis. Importantly, GnIH in birds and mammals appears to act at all levels of the hypothalamo-pituitary-gonadal (HPG) axis, and possibly over different time-frames (minutes-days). Thus, GnIH and its homologs appear to act as key neurohormones controlling vertebrate reproduction. The discovery of GnIH has enabled us to understand and manipulate vertebrate reproduction from an entirely new perspective. © 2010 Elsevier Inc.

Phylogenetic aspects of gonadotropin-inhibitory hormone and its homologs in vertebrates

Tsutsui, Kazuyoshi

Annals of the New York Academy of Sciences1200p.75 - 842010年07月-2010年07月 

PubMedDOIScopus

詳細

ISSN:00778923

概要:The decapeptide gonadotropin-releasing hormone (GnRH) is the primary factor responsible for the hypothalamic control of gonadotropin secretion in vertebrates, but a hypothalamic neuropeptide inhibiting gonadotropin secretion was, until recently, unknown in vertebrates. In 2000, we discovered a novel hypothalamic dodecapeptide that inhibits gonadotropin release in quail and termed it gonadotropin-inhibitory hormone (GnIH). GnIH acts on the pituitary and GnRH neurons in the hypothalamus via a novel G protein-coupled receptor for GnIH to inhibit gonadal development and maintenance by decreasing gonadotropin release and synthesis. The pineal hormone melatonin is a key factor controlling GnIH neural function. Because GnIH exists and functions in several avian species, GnIH is considered to be a new key neuropeptide controlling avian reproduction. After the discovery of GnIH in birds, the presence of GnIH homologs has been demonstrated in other vertebrates from fish to humans. Interestingly, mammalian GnIH homologs also act to inhibit reproduction by decreasing gonadotropin release in several mammalian species. It is concluded that GnIH and GnIH homologs act to inhibit gonadotropin release in higher vertebrates. © 2010 New York Academy of Sciences.

Identification of gonadotropin-inhibitory hormone in the zebra finch (Taeniopygia guttata): Peptide isolation, cDNA cloning and brain distribution

Tobari, Yasuko; Iijima, Norio; Tsunekawa, Kenta; Osugi, Tomohiro; Okanoya, Kazuo; Tsutsui, Kazuyoshi; Ozawa, Hitoshi

Peptides31(5)p.816 - 8262010年05月-2010年05月 

PubMedDOIScopus

詳細

ISSN:01969781

概要:Two novel RFamide peptides, kisspeptins and gonadotropin-inhibitory hormone (GnIH) are neuropeptides that appear critical in the regulation of the reproductive neuroendocrine axis. GnIH was first identified in avian brain, however, kisspeptins have not been identified in birds. To determine biochemically the presence of kisspeptins and GnIH in the zebra finch, a study was conducted to isolate these two peptides from zebra finch brain. Peptides were isolated by immunoaffinity purification and only one peptide was characterized by mass spectrometry. This peptide was confirmed to be a 12-amino acid sequence with RFamide at its C-terminus; its sequence is SIKPFSNLPLRFamide (zebra finch GnIH). By this approach, however, identification of kisspeptin from zebra finch brain was not achieved. Cloned zebra finch GnIH precursor cDNA encoded three peptides that possess characteristic LPXRFamide (X = L or Q) motifs at the C-termini. In situ hybridization and immunohistochemical analysis revealed the cellular localization of zebra finch GnIH mRNA and peptide in the paraventricular nucleus and the dorsomedial nucleus of the hypothalamus. Fluorescent immunohistochemistry with confocal microscopy indicated that GnIH-immunoreactive (ir) fibers are very close appositions with gonadotropin-releasing hormone-I (GnRH-I) cells. Furthermore GnIH-ir nerve fibers were widely distributed in the multiple brain regions including the septum, preoptic area, median eminence, optic tectum and median eminence. The prominent fibers were seen in the ventral tegmental area, midbrain central gray and dorsal motor nucleus of the vagus in the medulla. Thus, GnIH may participate in not only neuroendocrine functions but also regulation of motivation for social behavior and autonomic mechanisms. © 2010 Elsevier Inc.

Prolactin increases the synthesis of 7α-hydroxypregnenolone, a key factor for induction of locomotor activity, in breeding male newts

Haraguchi, Shogo; Koyama, Teppei; Hasunuma, Itaru; Vaudry, Hubert; Tsutsui, Kazuyoshi

Endocrinology151(5)p.2211 - 22222010年05月-2010年05月 

PubMedDOIScopus

詳細

ISSN:00137227

概要:We recently found that the Japanese red-bellied newt, Cynops pyrrhogaster, actively produces 7α-hydroxypregnenolone, a previously undescribed amphibian neurosteroid. 7α-Hydroxypregnenolone stimulates locomotor activity of male newts. Locomotor activity of male newts increases during the breeding period as in other wild animals, but the molecular mechanism for such a change in locomotor activity is poorly understood. Here we show that the adenohypophyseal hormone prolactin (PRL) stimulates 7α-hydroxypregnenolone synthesis in the brain, thus increasing locomotor activity of breeding male newts. In this study, cytochrome P4507α (CYP7B), a steroidogenic enzyme catalyzing the formation of 7α-hydroxypregnenolone, was first identified to analyze seasonal changes in 7α-hydroxypregnenolone synthesis. Only males exhibited marked seasonal changes in 7α- hydroxypregnenolone synthesis and CYP7B expression in the brain, with a maximum level in the spring breeding period when locomotor activity of males increases. Subsequently we identified PRL as a key component of the mechanism regulating 7α-hydroxypregnenolone synthesis. Hypophysectomy decreased 7α-hydroxypregnenolone synthesis in the male brain, whereas administration of PRL but not gonadotropins to hypophysectomized males caused a dose-dependent increase in 7α-hydroxypregnenolone synthesis. To analyze the mode of PRL action,CYP7Bandthe receptor for PRLwerelocalized in the male brain. PRL receptorwasexpressed in the neurons expressing CYP7B in the magnocellular preoptic nucleus. Thus, PRL appears to act directly on neurosteroidogenic magnocellular preoptic nucleus neurons to regulate 7α-hydroxypregnenolone synthesis, thus inducing seasonal locomotor changes in male newts. This is the first report describing the regulation of neurosteroidogenesis in the brain by an adenohypophyseal hormone in any vertebrate. Copyright © 2010 by The Endocrine Society.

Identification, localization, and function of a novel avian hypothalamic neuropeptide, 26RFa, and its cognate receptor, G protein-coupled receptor-103

Ukena, Kazuyoshi; Tachibana, Tetsuya; Iwakoshi-Ukena, Eiko; Saito, Yumiko; Minakata, Hiroyuki; Kawaguchi, Ryoko; Osugi, Tomohiro; Tobari, Yasuko; Leprince, Jérôme; Vaudry, Hubert; Tsutsui, Kazuyoshi

Endocrinology151(5)p.2255 - 22642010年05月-2010年05月 

PubMedDOIScopus

詳細

ISSN:00137227

概要:Several neuropeptides with the C-terminal RFamide sequence have been identified in the hypothalamus of a variety of vertebrates. Among the RFamide peptide groups, however, only LPXRFamide peptides, including gonadotropin-inhibitory hormone, have been characterized in the avian brain. In the present study, we sought for the presence of other RFamide peptides in the avian hypothalamus. We identified a cDNA encoding an RFamide peptide orthologous to 26RFa (also referred to as QRFP) in thehypothalamusof the Japanese quail.Thededucedquail26RFaprecursor consisted of 120-amino-acid residues, encoding one RFamide peptide with 27 amino acids. This RFamide peptide was flanked at the N terminus by a dibasic amino acid cleavage site and at the C terminus by a glycine amidation signal. Quantitative RT-PCR analysis demonstrated specific expression of quail 26RFa mRNA in the diencephalon including the hypothalamus. Furthermore, mass spectrometry analysis revealed the presence of a peptide exhibiting the mass of mature 26RFa, indicating that the peptide is actually produced from the precursor in the diencephalon. 26RFa-producing cell bodies were localized in the anterior hypothalamic nucleus in the brain. Synthetic 26RFa increased intracellular Ca2+ concentration in HEK293T cells transfected with the chicken G protein-coupled receptor GPR103. Intracerebro-ventricular injection of 26RFa in broiler chicks stimulated feeding behavior. These data provide the first evidence for the occurrence of the peptide 26RFa in the avian hypothalamus and indicate that this peptide exerts orexigenic activity. Copyright © 2010 by The Endocrine Society.

総説:性周期とニューロペプチド: GnIH 特集「ニューロペプチド」Hormone Frontier in Gynecology

筒井和義・産賀崇由

メディカルレビュー社17p.25 - 292010年-

GnIHによるゴナドトロピン分泌制御 特集/生殖機能調節の新しい視点

筒井和義

産科と婦人科 (Obstet. Gynecol.; 診断と治療社)77p.252 - 2582010年-

Melatonin Stimulates the Release of Gonadotropin-Inhibitory Hormone by the Avian Hypothalamus

Chowdhury, Vishwajit S.;Yamamoto, Kazutoshi;Ubuka, Takayoshi;Bentley, George E.;Hattori, Atsuhiko;Tsutsui, Kazuyoshi

ENDOCRINOLOGY151(1)p.271 - 2802010年-2010年

DOIWoS

詳細

ISSN:0013-7227

Salt-sensitive hypertension in circadian clock-deficient Cry-null mice involves dysregulated adrenal Hsd3b6

Doi, Masao;Takahashi, Yukari;Komatsu, Rie;Yamazaki, Fumiyoshi;Yamada, Hiroyuki;Haraguchi, Shogo;Emoto, Noriaki;Okuno, Yasushi;Tsujimoto, Gozoh;Kanematsu, Akihiro;Ogawa, Osamu;Todo, Takeshi;Tsutsui, Kazuyoshi;van der Horst, Gijsbertus T. J.;Okamura, Hitoshi

NATURE MEDICINE16(1)p.67 - 742010年-2010年

DOIWoS

詳細

ISSN:1078-8956

RFamide-Related Peptide and Messenger Ribonucleic Acid Expression in Mammalian Testis: Association with the Spermatogenic Cycle

Zhao, Sheng;Zhu, Edward;Yang, Christina;Bentley, George E.;Tsutsui, Kazuyoshi;Kriegsfeld, Lance J.

ENDOCRINOLOGY151(2)p.617 - 6272010年-2010年

DOIWoS

詳細

ISSN:0013-7227

Temporal Phase Relation of Circadian Neural Oscillations Alters RFamide-Related Peptide-3 and Testicular Function in the Mouse

Sethi, Sumit;Tsutsui, Kazuyoshi;Chaturvedi, Chandra Mohini

NEUROENDOCRINOLOGY91(2)p.189 - 1992010年-2010年

DOIWoS

詳細

ISSN:0028-3835

Photoperiod and Reproductive Condition Are Associated with Changes in RFamide-Related Peptide (RFRP) Expression in Syrian Hamsters (Mesocricetus auratus)

Mason, Alex O.;Duffy, Sean;Zhao, Sheng;Ubuka, Takayoshi;Bentley, George E.;Tsutsui, Kazuyoshi;Silver, Rae;Kriegsfeld, Lance J.

JOURNAL OF BIOLOGICAL RHYTHMS25(3)p.176 - 1852010年-2010年

DOIWoS

詳細

ISSN:0748-7304

The unique contribution of amphibians to the discovery of novel neuropeptides

Vaudry, Hubert;Leprince, Jerome;Do Rego, Jean-Claude;Tonon, Marie-Christine;Tsutsui, Kazuyoshi;Conlon, J. Michael

ENDOCRINE JOURNAL57p.S234 - S2342010年-2010年

WoS

詳細

ISSN:0918-8959

Novel hypothalamic peptides and receptors in a basal vertebrate, the sea lamprey

Sower, Stacia A.;Kavanaugh, Scott I.;Kosugi, Takayoshi;Aquilina-Beck, Allisan;Osugi, Tomohiro;Tsutsui, Kazuyoshi

ENDOCRINE JOURNAL57p.S234 - S2342010年-2010年

WoS

詳細

ISSN:0918-8959

Discovery and functional significance of gonadotropin-inhibitory hormone (GnIH) in vertebrates: From comparative to general

Tsutsui, Kazuyoshi;Chowdhury, Vishwajit S.;Osugi, Tomohiro;Ubuka, Takayoshi;Bentley, George E.;Kriegsfeld, Lance J.;Matsuzaki, Toshiya;Iwasa, Takeshi;Irahara, Minoru;Sower, Stacia A.;Vaudry, Hubert

ENDOCRINE JOURNAL57p.S234 - S2352010年-2010年

WoS

詳細

ISSN:0918-8959

Age-dependent variation in the RFRP-3 neurons is inversely correlated with gonadal activity of mice

Sethi, Sumit;Tsutsui, Kazuyoshi;Chaturvedi, Chandra Mohini

GENERAL AND COMPARATIVE ENDOCRINOLOGY168(3)p.326 - 3322010年-2010年

DOIWoS

詳細

ISSN:0016-6480

Differential Expression Patterns of GnRH and GnIH in Ovary of Mouse During Estrous Cycle

Singh, Padmasana;Krishna, Amitabh;Sridaran, Rajagopala;Tsutsui, Kazuyoshi

BIOLOGY OF REPRODUCTIONp.184 - 1842010年-2010年

WoS

詳細

ISSN:0006-3363

Recent studies of gonadotropin-inhibitory hormone (GnIH) in the mammalian hypothalamus, pituitary and gonads

Bentley, George E.;Tsutsui, Kazuyoshi;Kriegsfeld, Lance J.

BRAIN RESEARCH1364p.62 - 712010年-2010年

DOIWoS

詳細

ISSN:0006-8993

Temporal phase relation of circadian neural oscillations alters RFamide-related peptide-3 (RFRP-3), a mammalian gonadotropin-inhibitory hormone (GnIH) homolog, and testicular function in the mouse (Mus musculus)

S. Sethi, K. Tsutsui and C. M. Chaturvedi

Neuroendocrinology91p.189 - 1992010年-

Identification of human gonadotropin-inhibitory hormone homologs, RFRP-1 and RFRP-3, and the cognate receptor, GPR147 in the human hypothalamic pituitary axis.

T. Ubuka, K. Morgan, A. J. Pawson, T. Osug, V. S. Chowdhury, H. Minakata, K. Tsutsui, R. P. Millar and George E. Bentley

PLoS ONE4p.e84002009年-

Gonadotropin-inhibitory hormone identification, cDNA cloning, and distribution in rhesus macaque brain.

T. Ubuka, H. Lai, M. Kitani, A. Suzuuchi, V. Pham, P. A. Cadigan, V. S. Chowdhury, K. Tsutsui and G. E. Bentley

J. Comp. Neurol517p.841 - 8552009年-

Molecular evolution of multiple forms of kisspeptins and GPR54 receptors in vertebrates.

Y. R. Lee, K. Tsunekawa, M. J. Moon, H. N. Um, J-I. Hwang, T. Osugi, N. Otaki, Y. Sunakawa, K. Kim, H. Vaudry, H. B. Kwon, J. Y. Seong and K. Tsutsui

Endocrinology150p.2837 - 28462009年-

Review: A new key neurohormone controlling reproduction, gonadotropin-inhibitory hormone (GnIH): Biosynthesis, mode of action and functional significance.

K. Tsutsui

Prog. Neurobiol.88p.76 - 882009年-

Review: Evolutionary origin and divergence of GnIH and its homologous peptides

K. Tsutsui and T. Osugi

Gen. Comp. Endocrinol.161p.30 - 332009年-

Review: Neurosteroid biosynthesis : enzymatic pathways and neuroendocrine regulation by neurotransmitters and neuropeptides.

J. L. Do Rego, J. Y. Seong, D. Burel, J. Leprince, V. Luu-The, M.-C. Tonon, G. Pelletier, K.Tsutsui and Hubert Vaudry

Front. Neuroendocrinol30p.259 - 3012009年-

Review: Steroid Biosynthesis within the frog brain : A model of neuroendocrine regulation.

J. L. Do Rego, J. Y. Seong, V. Luu-The, K. Tsutsui, G. Pelletier, M.-C. Tonon and H. Vaudry

Ann. N.Y. Acad. Sci.1163p.83 - 922009年-

Review: Hormone-mediated reproductive behavior in the red-bellied newt.

S. Kikuyama, I. Hasunuma, F. Toyoda, S. Haraguchi and K. Tsutsui

Ann. N.Y. Acad. Sci.1163p.179 - 1862009年-

Review: Identification, biosynthesis and function of 7alpha-hydroxypregnenolone, a new key neurosteroid controlling locomotor activity, in non-mammals.

K. Tsutsui, S. Haraguchi, K. Inoue, H. Miyabara, S. Suzuki, Y. Ogura, T. Koyama, M. Matsunaga and H. Vaudry

Ann. N.Y. Acad. Sci.1163p.308 - 3152009年-

Seasonal changes in the synthesis of 7alpha-hydroxypregnenolone stimulating locomotor activity in newts.

S. Haraguchi, T. Koyama and J. L. Do Rego and K. Tsutsui

Ann. N.Y. Acad. Sci.1163p.410 - 4132009年-

Diurnal changes in the synthesis of 7alpha-hydroxypregnenolone stimulating locomotor activity in newts.

T. Koyama, S. Haraguchi, H. Vaudry and K. Tsutsui

Ann. N. Y. Acad. Sci.1163p.444 - 4472009年-

Review: A new key neurohormone controlling reproduction, gonadotropin-inhibitory hormone (GnIH) in birds: discovery, progress and prospect.

K. Tsutsui, E. Saigoh, H. Yin, T. Ubuka, V. S. Chowdhury, T. Osugi, K. Ukena, P. J. Sharp, J. C. Wingfield and G. E. Bentley

J. Neuroendocrinol21p.271 - 2752009年-

Review: Neurosteroid biosynthesis and action in the Purkinje cell.

K. Tsutsui

J. Exp. Neurosci.2p.1 - 122009年-

メラトニンに関する最近の話題:メラトニンとGnIH、Annual Review 糖尿病・代謝・内分泌2009

筒井和義

中外医学社 V. 生殖医学p.190 - 1952009年-

メラトニンとGnIHの光周性

筒井和義

「光周性の分子生物学」p.149 - 1572009年-

Review: Discovery of a novel avian neurosteroid, 7α-hydroxypregnenolone, and its role in the regulation of the diurnal rhythm of locomotor activity in Japanese quail

K. Tsutsui, K. Inoue, H. Miyabara, S. Suzuki, Y. Ogura, Y. Tobari and S. Haraguchi

Gen. Comp. Endocrinol.163p.117 - 1222009年-

Review: Proximate and ultimate mechanisms driving circadian control of neuroendocrine function: Lessons from the young and old

W. P. Williams III, E. M. Gibson, C. Wang, S. Tjho, N. Khattar, G. E. Bentley, K. Tsutsui and L. J. Kriegsfeld

Integr. Comp. Biol.49p.519 - 5372009年-

Review: GnIH: A Multifunctional Neuropeptide

G. E. Bentley, T. Ubuka, N. L. McGuire, R. Calisi, N. Perfito, L. J. Kriegsfeld, J. C. Wingfield and K. Tsutsui

J. Neuroendocrinol.21p.276 - 2812009年-

Review: Octopus GnRH (oct-GnRH), a multifunctional peptide in the endocrine and nervous systems of the cephalopod

H. Minakata, S. Shigeno, N. Kano, S. Haraguchi, T. Osugi and K. Tsutsui

J. Neuroendocrinol.21p.322 - 3262009年-

7α-Hydroxypregnenolone mediates melatonin action underlying diurnal locomotor rhythms.

K. Tsutsui, K. Inoue, H. Miyabara, S. Suzuki, Y. Ogura and S. Haraguchi

J Neuroscience28p.2158 - 21672008年-

Alterations in RFamide-related peptide expression are coordinated with the preovulatory luteinizing hormone surge.

E. M. Gibson, S. A. Humber, S. Jain, W. P. Williams III, S. Zhao, G. E. Bentley, K. Tsutsui and L. J. Kriegsfeld

Endocrinology149p.4958 - 49692008年-

Auditory stimulation of reproductive function in male Rufous-winged Sparrows, Aimophila carpalis.

T. W. Small, P. J. Sharp, G. E. Bentley, R. P. Millar, K. Tsutsui, C. Strand and P. Deviche

Horm. Behav.53p.28 - 392008年-

Changes in GnRH I, bradykinin and their receptors and GnIH in the ovary of Calotes versicolor during reproductive cycle.

P. Singh, A. Krishna, R. Sridaran and K. Tsutsui

Gen.Comp. Endocrinol159p.158 - 1692008年-

Gonadotropin-inhibitory hormone (GnIH): biosynthesis, mode of action and functional significance in birds.

K. Tsutsui and G. E. Bentley

Avian Biol. Res.1p.175 - 1862008年-

Gonadotropin-inhibitory hormone and its receptor in the avian reproductive system.

G. Bentley, T. Ubuka; N. L. McGuire, V. S. Chowdhury, Y. Morita, T. Yano, I. Hasunuma, M. Binns, J. C. Wingfield and K. Tsutsui

Gen. Comp. Endocrinol.156p.34 - 432008年-

Gonadotropin-inhibitory hormone neurons interact directly with gonadotropin-releasing hormone-I and -II neurons in European starling brain.

T. Ubuka, S. Kim, Y. Huang, J. Reid, J. Jiang, T. Osugi, V. S. Chowdhury, K. Tsutsui and Bentley G. E.

Endocrinology149p.268 - 2782008年-

Hypophysiotropic role of RFamide-related peptide-3 in the inhibition of LH secretion in female rats.

M. Murakami, T. Matsuzaki, T. Iwasa, T. Yasui, M. Irahara, T. Osugi and K. Tsutsui

J. Endocrinol.199p.105 - 1122008年-

Immunohistochemical detection and biological activities of CYP17 (P450c17) in the indifferent gonad of the frog Rana rugosa.

N. Sakurai, K. Maruo, S. Haraguchi, Y. Uno, Y. Oshima, K. Tsutsui, Y. Matsuda, J. L. Do Rego, G. Pelletier, H. Vaudry and M. Nakamura

J. Steroid Biochem. Mol. Biol.112p.5 - 122008年-

Melatonin stimulates the release of growth hormone and prolactin by inducing the expression of frog growth hormone-releasing peptide (fGRP) and its related peptide-2 (fGRP-RP-2) in the amphibian hypothalamus.

V. S. Chowdhury, K. Yamamoto, I. Saeki, I. Hasunuma, T. Shimura and K. Tsutsui

Endocrinology149p.962 - 9702008年-

Photoperiod-independent hypothalamic regulation of luteinizing hormone secretion in a free-living Sonoran desert bird, the Rufous-winged Sparrow (Aimophila carpalis).

T. W. Small, P. J. Sharp, G. E. Bentley, R. P. Millar, K. Tsutsui, E. Mura and P. Deviche

Brain Behav. Evol.71p.127 - 1422008年-

Potent action of RFRP-3 on pituitary gonadotropes indicative of an hypophysiotropic role in the negative regulation of gonadotropin secretion.

I. J. Clarke, I. P. Sari, Y. Qi, J. T. Smith, H. C. Parkington, T. Ubuka, J. Iqbal, Q. Li, A. Tilbrook, K. Morgan, A. J. Pawson, K. Tsutsui, R. P. Millar and G. E. Bentley

Endocrinology149p.5811 - 58212008年-

Review: Neurosteroids in the Purkinje cell: Biosynthesis, mode of action and functional significance.

K. Tsutsui

Mol. Neurobiol.37p.116 - 1252008年-

Review: Progesterone biosynthesis and action in the developing neuron.

K. Tsutsui

Endocrinology149p.2757 - 27612008年-

Review: Recent advances in reproductive neuroendocrinology: A role for the RFamide peptides in seasonal reproduction?

T. J. Greives, L. J. Kriegsfeld, G. E. Bentley, K. Tsutsui and G. E. Demas

Proc. R. Soc. B275p.1943 - 19512008年-

The orexigenic effect of GnIH is mediate by central opioid receptors in chicks.

T. Tachibana, N. Masuda, K. Tsutsui, K. Ukena and H. Ueda

Comp. Biochem. Physiol. A Mol. Integr. Physiol.150p.21 - 252008年-

Neurosteroid synthesis and action in the cerebellum during development

K. Tsutsui

In: a special issue for "Cerebellum, a target for hormonal signaling". Cerebellum7p.502 - 5042008年-

Review: Expression, localization and possible actions of 25-Dx, a membrane-associated putative progesterone-binding protein, in the developing Purkinje cell of the cerebellum: A new insight into the biosynthesis, metabolism and multiple actions of progesterone as a neurosteroid.

H. Sakamoto, K. Ukena, M. Kawata and K. Tsutsui

Cerebellum7p.18 - 252008年-

生殖神経内分泌学の新たな展開:GnIHとキスペプチンの発見

筒井和義

増刊号「ホルモンの病態異常と臨床検査」52p.12072008年-

GnIHとGnIH同属ペプチド(LPXRFamideペプチド):構造と機能の普遍性と多様性

筒井和義

生化学80p.849 - 8542008年-

総説:ステロイドのnon-genomic action

徳元 俊伸・筒井 和義

特集:合成ステロイドホルモン -最新の基礎・臨床研究-66p.70 - 762008年-

Review: The general and comparative biology of gonadotropin-inhibitory hormone (GnIH).

K. Tsutsui, T. Ubuka, E. Saigoh, H.Yin, T. Osugi, K. Inoue, V. S. Chowdhury, K. Ukena, N. Ciccone, P. J. Sharp, J. C. Wingfield and G. E. Bentley

Gen. Comp. Endocrinol.153p.365 - 3702007年08月-2007年09月 

DOI

Cerebellum, a target for hormonal signaling

N. Koibuchi, J. Kimura-Kuroda, Y. Ikeda and K. Tsutsui

Cerebellum7p.499 - 5042007年-

Mode of action and functional significance of estrogen inducing dendritic growth, spinogenesis and synaptogenesis in the developing Purkinje cell.

K. Sasahara, H. Shikimi, S. Haraguchi, H. Sakamoto, S. Honda, N. Harada and K. Tsutsui

J Neuroscience27p.7408 - 74172007年-

Rat RFamide-related peptide-3 stimulates GH secretion, inhibits LH secretion, and has variable effects on sex behavior in the adult male rat.

M. A. Johnson, K. Tsutsui and G. S. Fraley

Horm Behav.51p.171 - 1802007年-

Comparative reproductive neuroendocrinology.

P.J. Sharp and K. Tsutsui

Gen. Comp. Endocrinol.153p.344 - 3452007年-

Review: Discovery of gonadotropin-inhibitory hormone in a domesticated bird, its mode of action and functional significance.

K. Tsutsui, T. Ubuka, H. Yin, T. Osugi, K. Ukena, G. E. Bentley, P. J. Sharp and J. C. Wingfield

J. Ornithol.148p.S515 - S5262007年-

Review: Gonadotropin-inhibitory hormone in seasonally-breeding songbirds: Neuroanatomy and functional biology.

G. E. Bentley, N. Perfito, T. Ubuka, K. Ukena, T. Osugi, S. O’Brien, K. Tsutsui and J. C. Wingfield

J. Ornithol.148p.S521 - S5262007年-

Melatonin action on neuropeptide induction through receptor-mediated mechanisms in the brain.

K. Tsutsui, T. Ubuka and G. E. Bentley

In: Melatonin: From Molecules to Therapy,p.387 - 4002007年-

Gonadotropin-inhibitory hormone (GnIH) in the avian brain.

K. Tsutsui

In: Hormone Biotechnology,p.266 - 2722007年-

Neuronal neurosteroidogenesis and organizing actions of neurosteroids during cerebellar development.

K. Tsutsui

In: Evolutionary Molecular Strategies and Plasticity,p.169 - 1862007年-

総説:GnIH 特集/中枢内分泌の最新知見とその異常

筒井和義

産科と婦人科74p.904 - 9132007年-

脳ホルモンの新領域

筒井和義・浮穴和義・南方宏之

シリーズ21世紀の動物科学 10 内分泌と生命現象p.137 - 1752007年-

Control of luteinizing hormone and testosterone secretion in a flexibly breeding male passerine, the Rufous-winged Sparrow, Aimophila carpalis.

P. J. Deviche, T. Small, P. J. Sharp and K. Tsutsui

Gen. Comp. Endocrinol.149p.226 - 2352006年-

Evolutionary origin and divergence of PQRFamide peptides and LPXRFamide peptides in the RFamide peptide family: Insights from novel lamprey RFamide peptides.

T. Osugi, K. Ukena, S. A. Sower, H. Kawauchi and K. Tsutsui

FEBS Journal273p.1731 - 17432006年-

Gonadotropin-inhibitory hormone in birds: possible mode of action.

G. E. Bentley, N. Perfito, I. Moor, K. Ukena, K. Tsutsui and J. C. Wingfield

Acta Zool Sinica.52p.178 - 1822006年-

Gonadotropin-inhibitory hormone inhibits gonadal development and maintenance by decreasing gonadotropin synthesis and release in male quail.

T. Ubuka, K. Ukena, P. J. Sharp, G. E. Bentley and K. Tsutsui

Endocrinology147p.1187 - 11942006年-

Identification and characterization of a gonadotropin-inhibitory system in the brains of mammals.

L. J. Kriegsfeld, D. F. Mei, G. E. Bentley, T. Ubuka, A. A. Mason, K. Inoue, K. Ukena, K. Tsutsui and R. Silver

Proc. Natl. Acad. Sci. USA103p.2410 - 24152006年-

Mode of action and functional significance of avian gonadotropin-inhibitory hormone (GnIH).

K. Tsutsui, T. Ubuka, H. Yin, T. Osugi, K. Ukena, G. E. Bentley, N. Ciccone, K. Inoue, V. S. Chowdhury, P. J. Sharp and J. C. Wingfield

A review. J. Exp. Zool.305Ap.801 - 8062006年-

Molecular cloning and functional characterization of a prolactin-releasing peptide homolog from Xenopus laevis.

T. Sakamoto, A. Oda, K. Yamamoto, M. Kaneko, S. Kikuyama, A. Nishikawa, A. Takahashi, H. Kawauchi, K. Tsutsui and M. Fujimoto

Peptides27p.3347 - 33512006年-

Neural interaction of gonadotropin-regulating hormone immunoreactive neurons and the suprachiasmatic nucleus with the paraventricular organ in the Japanese grass lizard (Takydromus tachydromoides).

E. Kawano, Y. Takahata, T. Oishi, K. Ukena, K. Tsutsui and S. Tamotsu

Zool Sci.23p.277 - 2872006年-

Neurosteroid biosynthesis in the quail brain: A review.

K. Tsutsui, M. Matsunaga, H. MiyabaraI and K. Ukena

J. Exp. Zool.305Ap.733 - 7422006年-

Novel fish hypothalamic neuropeptides stimulate the release of gonadotropins and growth hormone from the pituitary of sockeye salmon.

M. Amano, S. Moriyama, M. Iigo, S. Kitamura, N. Amiya, K. Yamamori, K. Ukena and K. Tsutsui

J. Endocrinology188p.417 - 4232006年-

Rapid inhibition of female sexual behavior by gonadotropin-inhibitory hormone (GnIH).

G. E. Bentley, J. P. Jensen, G. J. Kaur, D. W. Wacker, K. Tsutsui and J. C. Wingfield

Horm. Behav.49p.550 - 5552006年-

Review: Biosynthesis and organizing action of neurosteroids in the developing Purkinje cell.

K. Tsutsui

Cerebellum5p.89 - 962006年-

Review: Biosynthesis, mode of action and functional significance of neurosteroids in the developing Purkinje cell.

K. Tsutsui

J. Steroid Biochem. Mol. Biol.102p.187 - 1942006年-

Review: Gonadotropin-inhibitory hormone (GnIH): Discovery, progress and perspective.

K. Tsutsui

J. Poult. Sci43p.191 - 1982006年-

Review: Hypothalamic LPXRF-amide peptides in vertebrates: Identification, localization and hypophysiotropic activity.

K. Tsutsui and K. Ukena

Peptides27p.1121 - 11292006年-

Review: Interactions of gonadotropin-releasing hormone (GnRH) and gonadotropin-inhibitory hormone (GnIH) in birds and mammals.

G. E. Bentley, L. J. Kriegsfeld, T. Osugi, K. Ukena, S. O’Brien, N. Perfito, I. Moore, K. Tsutsui and J. C. Wingfield

J. Exp. Zool.305Ap.807 - 8142006年-

Review: Neurosteroids in the brain neuron: Biosynthesis, action and medicinal impact on neurodegenerative disease.

K. Tsutsui and S. H. Mellon

Central Nervous System Agents in Medicinal Chemistry6p.73 - 822006年-

Structures and diverse functions of frog growth hormone-releasing peptide (fGRP) and its related peptides (fGRP-RPs): A review.

K. Ukena, A. Koda, K. Yamamoto, E. Iwakoshi-Ukena, H. Minakata, S. Kikuyama and K. Tsutsui

J. Exp. Zool.305Ap.815 - 8212006年-

Endocrinology of reproduction.

G. E. Bentley, K. Tsutsui and J. C. Wingfield

In: Reproductive Biology and Phylogeny of Birds,p.181 - 2422006年-

Avian gonadotropin-inhibitory hormone (GnIH): Identification, mode of action and functional significance.

K. Tsutsui

In: Comparative Endocrinology and Biodiversity in Asia and Oceania,p.197 - 2012006年-

Melatonin action on the induction of gonadotropin-inhibitory hormone in the avian brain.

V. S. Chowdhury, T. Ubuka, G. E. Bentley, K. Ukena, J. C. Wingfield and K. Tsutsui

In: Comparative Endocrinology and Biodiversity in Asia and Oceania,p.247 - 2502006年-

The RFamide-related peptides.

N. Chartrel, K. Tsutsui, J. Costentin and H. Vaudry

In: The Handbook of Biologically Active Peptides,p.799 - 8062006年-

総説:鳥類における脳の性分化機構

筒井和義・加藤真樹・岡ノ谷一夫

ホルモンと臨床54p.13 - 202006年-

総説:脳が合成するニューロステロイドと脳の自立的性分化機構

筒井和義

特集 ♂と♀のバイオロジー:生物の多様な性分化の仕組み25p.388 - 3922006年-

A novel G protein-coupled receptor for gonadotropin-inhibitory hormone in the Japanese quail (Coturnix japonica): identification, expression and binding activity.

H. Yin, K. Ukena, T. Ubuka and K. Tsutsui

J. Endocrinology184p.257 - 2662005年-

Expression of aromatase mRNA in the abdominal gland of the newt, Cynops pyrrhogaster.

Y. Ito, A. Hirota, M. Nakamura, M. Matsunaga, K. Tsutsui and S. Kikuyama

Ann. N. Y. Acad. Sci.1040p.348 - 3502005年-

Gonadotropin-inhibiting hormone stimulates feeding behavior in chicks.

T. Tachibana, M. Sato, H. Takahashi, K. Ukena, K. Tsutsui and M. Furuse

Brain Res.1050p.94 - 1002005年-

Melatonin induces the expression of gonadotropin-inhibitory hormone in the avian brain.

T. Ubuka, G. E. Bentley, K. Ukena, J. C. Wingfield and K. Tsutsui

Proc. Natl. Acad. Sci. USA, Nature Reviews Highlight102p.3052 - 30572005年-

Review: A new member of the hypothalamic RF-amide peptide family, LPXRF-amide peptides: Structure, localization and function.

K. Ukena and K. Tsutsui

Mass Spectrometry Reviews24p.469 - 4862005年-

Review: Gonadotropin-inhibitory hormone (GnIH).

K. Tsutsui

Jpn. J. Reprod. Endocrinol.10p.49 - 532005年-

The steroidogenic enzyme P450scc is expressed in oligodendrocyte progenitors during CNS remyelination.

C. Ibanez, K. Tsutsui, S. Kominami, M. Schumacher, E.-E. Baulieu and R. J.M. Franklin

Neuroreportin press2005年-

Structure, action and functional significance of GnIH.

K Tsutsui, G Bentley and N Ciccone

In: Functional Avian Endocrinology,p.73 - 822005年-

総説:発達期の小脳プルキンエ細胞における25-Dxの発現—プルキンエ細胞が合成するプロゲステロンの作用機構—

筒井和義・坂本浩隆・浮穴和義

生体の科学56p.296 - 3022005年-

7α-Hydroxypregnenolone acts as a neuronal activator to stimulate locomotor activity of breeding newts by means of the dopaminergic system.

M. Matsunaga, K. Ukena, E.-E. Baulieu and K. Tsutsui

Proc. Natl. Acad. Sci. USA101p.17282 - 172872004年-

Dendritic growth in response to environmental estrogens in the developing Purkinje cell.

H. Shikimi, H. Sakamoto, Y. Mezaki, K. Ukena and K. Tsutsui

Neurosci. Lett.364p.114 - 1182004年-

Does gonadotrophin inhibiting hormone (GnIH) play a functional role in avian reproduction?

N. A. Ciccone, K. Tsutsui, P. J. Sharp and I. C. Dunn

Br. Poult. Sci.45p.28 - 292004年-

Expression and distribution of octopus GnRH in the central nervous system and peripheral organs of the octopus (Octopus vulgaris) by in situ hybridization and immunohistochemistry.

E. Iwakoshi-Ukena, K. Ukena, K. Takuwa-Kuroda, A. Kanda, K. Tsutsui and H. Manakata

J. Comp. Neurol.477p.310 - 3232004年-

Expression and localization of 25-Dx, a membrane-associated putative progesterone-binding protein, in the developing Purkinje cell.

H. Sakamoto, K. Ukena, H. Takemori, M. Okamoto, M. Kawata and K. Tsutsui

Neuroscience126p.325 - 3342004年-

Gonadotrophin inhibitory hormone depresses gonadotrophin alpha and follicle-stimulating hormone beta subunit expression in the pituitary of the domestic chicken.

N.A. Ciccone, I.C. Dunn, T Boswell, K. Tsutsui, T. Ubuka, K. Ukena and P.J. Sharp

J. Neuroendocrinology16p.999 - 10062004年-

Gonadotropin-inhibitory hormone in Gambel’s white-crowned sparrow: cDNA identification, transcript localization and functional effects in laboratory and field experiments.

T. Osugi, K. Ukena, G. E. Bentley, S. O’Brien, I. T. Moore, J. C. Wingfield and K. Tsutsui

J. Endocrinology182p.33 - 422004年-

Identification of 3beta,5beta-tetrahydroprogesterone, a progesterone metabolite, and its stimulatory action on preoptic neurons in the avian brain.

M. Matsunaga, K. Okuhara, K. Ukena and K. Tsutsui

Brain Res.1007p.160 - 1662004年-

Photoperiodic response of serotonin- and galanin-immunoreactive neurons of the paraventricular organ and infundibular nucleus in Japanese quail, Coturnix coturnix japonica.

Y. Haida, T. Ubuka, K. Ukena, K. Tsutsui, T. Oishi and S. Tamotsu

Zool. Sci.21p.575 - 5822004年-

Review: Biosynthesis and action of neurosteroids.

K. Tsutsui

J. Reprod. Dev.50p.7 - 92004年-

Review: Organizing actions of neurosteroids in the Purkinje neuron.

K. Tsutsui, H. Sakamoto, H. Shikimi and Kazuyoshi Ukena

Neurosci. Res.49p.273 - 2792004年-

Classical and novel neurosteroids in vertebrate brains.

K. Tsutsui, M. Matsunaga, H. Miyabara, K. Ukena

In: Trends in Comparative Endocrinology,p.85 - 872004年-

A novel amphibian neurosteroid stimulating locomotor activity.

M. Matsunaga, K. Ukena, K. Tsutsui

In: Trends in Comparative Endocrinology,p.254 - 2562004年-

Novel avian neurosteroid: Identification of 7α-hydroxypregnenolone in the quail brain.

H. Miyabara, M. Matsunaga, K. Ukena, K. Tsutsui

In: Trends in Comparative Endocrinology,p.328 - 3302004年-

Synapse formation in response to estrogen synthesized de novo in the developing Purkinje cell.

H. Shikimi, H. Sakamoto, K. Ukena and K. Tsutsui

In: Trends in Comparative Endocrinology,p.319 - 3212004年-

Immunohistochemical localization of the neuropeptides in the paraventricular organ of the Japanese grass lizard, Takydromus tachydromoides.

E. Kawano, T. Oishi, K. Ukena, K. Tsutsui and S. Tamotsu

In: Trends in Comparative Endocrinology,p.331 - 3332004年-

Comparative aspects of novel hypothalamic LPXRF-amide peptides in the vertebrate brain: Structure, localization and function.

K. Ukena, K. Sawada, A. Kod, K. Yamamoto, S. Kikuyama, H. Satake, E. Iwakoshi-Ukena, H. Minakata, K. Tsutsui

In: Trends in Comparative Endocrinology,p.325 - 3272004年-

Identification and localization of a novel lamprey hypothalamic neuropeptide of the RF-amide peptide family.

T. Osugi, K. Ukena, M. Nozaki, H. Kawauchi, S. A. Sower and K. Tsutsui

In: Trends in Comparative Endocrinology,p.322 - 3242004年-

Effects of RF-amide peptides on the release of TSH from the bullfrog pituitary.

K. Yamamoto, A. Koda, K. Ukena, R. Okada, E. Iwakoshi-Ukena, H. Minakata, K. Tsutsui and S. Kikuyama

In: Trends in Comparative Endocrinology,p.298 - 3002004年-

ステロイドホルモン研究のフロンティア 総説:ニューロステロイドの合成と作用

筒井和義

化学と生物42p.681 - 6862004年-

A novel aspect of the cerebellum: Biosynthesis of neurosteroids in the Purkinje cell.

K. Tsutsui, K. Ukena and H. Sakamoto

Cerebellum2p.215 - 2222003年-

Biosynthesis and action of neurosteroids in the cerebellar Purkinje neuron.

K. Tsutsui, H. Sakamoto and K. Ukena

J. Steroid Biochem. Mol. Biol.85p.311 - 3212003年-

Cellular distribution and bioactivity of the key steroidogenic enzyme, cytochrome P450side chain cleavage, in sensory neural pathways.

C. Patte-Mensah, V. Kappes, M.-J. Freund-Mercier, K. Tsutsui, and A. G. Mensah-Nyagan

J. Neurochemistry86p.1233 - 12462003年-

Comparative aspects of neurosteroids: production and function.

K. Tsutsui and R. W. Lea

J. Physiology543p.7 - 92003年-

Dendritic growth and spine formation in response to estrogen in the developing Purkinje cell.

H. Sakamoto, Y. Mezaki, H. Shikimi, K. Ukena and K. Tsutsui

Endocrinology144p.4466 - 44772003年-

Developmental changes in gonadotropin-inhibitory hormone in the quail hypothalamo-hypophysial system.

T. Ubuka, M. Ueno, K. Ukena and K. Tsutsui

J. Endocrinology178p.311 - 3182003年-

Distribution of a novel avian gonadotropin-inhibitory hormone in the quail brain.

K. Ukena, T. Ubuka and K. Tsutsui

Cell Tissue Res.312p.73 - 792003年-

Gonadotropin-inhibitory peptide in song sparrows (Melospiza melodia) in different reproductive conditions, and in house sparrows (Passer domesticus) relative to chicken-gonadotropin-releasing hormone.

G. E. Bentley, N. Perfito, K. Ukena, K. Tsutsui and J. C. Wingfield

J. Neuroendocrinology15p.794 - 8022003年-

Neonatal expression of progesterone receptor isoforms in the cerebellar Purkinje cell in rats.

H. Sakamoto, H. Shikimi, K. Ukena and K. Tsutsui

Neurosci. Lett.343p.163 - 1662003年-

Review: Biosynthesis and action of neurosteroids in the cerebellar Purkinje neuron.

K. Tsutsui, H. Sakamoto and K. Ukena

J. Steroid Biochem. Mol. Biol.85p.311 - 3212003年-

Review: Biosynthesis and biological actions of neurosteroids in the avian brain.

K. Tsutsui, M. Matsunaga and K. Ukena

Avian Poultry Biol Reviews14p.63 - 782003年-

Review: Sex steroid communication in the ring dove brain during courtship.

M. D. C. Belle, K. Tsutsui and R. W. Lea

Can. J. Physiol. Pharmacol.81p.359 - 3702003年-

Seasonal changes in neurosteroids in the urodele brain and environmental factors inducing their changes.

Y. Inai, K. Ukena, K. Nagai, T. Oishi and K. Tsutsui

Brain Res.959p.214 - 2252003年-

Novel neuropeptides related to frog growth hormone-releasing peptide: Isolation, sequence, and functional analysis.

K. Ukena, A. Koda, K. Yamamoto, T. Kobayashi, E. Iwakoshi-Ukena, H. Minakata, S. Kikuyama and K. Tsutsui

Endocrinology144p.3879 - 38842003年-

総説:ニューロステロイドのシナプス形成誘導作用

筒井和義・坂本浩隆・浮穴和義・古川康雄

生体の科学54p.101 - 1082003年-

総説:ニューロンが合成するニューロステロイドのノンゲノミック作用とゲノミック作用

筒井和義・坂本浩隆・食見花子・浮穴和義

生殖内分泌学会雑誌8p.19 - 262003年-

総説:小脳プルキンエ細胞におけるニューロステロイドの合成と作用

筒井和義

ホルモンと臨床 増刊号:ステロイドホルモン研究の進歩52p.103 - 1102003年-

A novel amphibian hypothalamic neuropeptide: Isolation, localization and biological activity.

A. Koda, K. Ukena, H. Teranishi, S. Ohta, K. Yamamoto, S. Kikuyama and K. Tsutsui

Endocrinology143p.411 - 4192002年-

A novel rat hypothalamic RFamide-related peptide identified by immunoaffinity chromatography and mass spectrometry.

K. Ukena, E. Iwakoshi, H. Minakata and K. Tsutsui

FEBS Lett.512p.255 - 2582002年-

Androgen biosynthesis in the quail brain.

M. Matsunaga, K. Ukena and K. Tsutsui

Brain Res.948p.180 - 1852002年-

Deep brain photoreceptors and photoperiodism in vertebrates.

T. Oishi, Y. Haida, K. Okano, T. Yoshikawa,, E. Kawano, K. Nagai, Y. Fukada, K. Tsutsui and S. Tamotsu

J. Photosci.9p.5 - 82002年-

Dendritic spine formation in response to progesterone synthesized de novo in the developing Purkinje cell in rats.

H. Sakamoto, K. Ukena and K. Tsutsui

Neurosci. Lett.322p.111 - 1152002年-

Expression and localization of cytochrome P45011beta, aldo mRNA in the frog brain.

M. Takase, K. Ukena and K. Tsutsui

Brain Res.950p.288 - 2962002年-

Identification of a cDNA encoding a novel amphibian growth hormone-releasing peptide and localization of its transcript.

K. Sawada, K. Ukena, S. Kikuyama and K. Tsutsui

J. Endocrinology174p.395 - 4022002年-

Immunocytochemistry of serotonin and galanin in the hypothalamus of the Japanese quail.

Y. Haida, T. Oishi, K. Tsutsui and S. Tamotsu

J. Photosci.9p.258 - 2602002年-

Isolation and characterization of an octopus gonadotropin-releasing hormone.

E. Iwakoshi, K. Kuroda, Y. Fujisawa, M. Hisada, K. Ukena, H. Minakata and K. Tsutsui

Biochem. Biophys. Res. Commun.291p.1187 - 11932002年-

Novel fish hypothalamic neuropeptide: Cloning of a cDNA encoding the precursor polypeptide and identification and localization of the mature peptide.

K. Sawada, K. Ukena, H. Satake, E. Iwakoshi, H. Minakata and K. Tsutsui

Eur. J. Biochem.269p.6000 - 60082002年-

総説:ニューロンにおけるニューロステロイドの合成と作用

筒井和義

比較生理生化学19p.103 - 1102002年-

A novel hypothalamic neuropeptide: Gonadotropin-inhibitory hormone.

K. Tsutsui, K. Ukena, E. Saigoh, H. Teranishi, Y. Fujisawa, H. Satake, H. Minakata and P. J. Sharp

Internat. J. Mol. Med.8p.400 - 40052001年-

Activity and localization of 3beta-hydroxysteroid dehydrogenase/delta5-delta4-isomerase in the zebrafish central nervous system.

H. Sakamoto, K. Ukena and K. Tsutsui

J. Comp. Neurol.439p.291 - 3052001年-

Characterization of a cDNA encoding a novel avian hypothalamic neuropeptide exerting an inhibitory effect on gonadotropin release.

H. Satake, M. Hisada, T. Kawada, H. Minakata, K. Ukena and K. Tsutsui

Biochemical J.354p.379 - 3852001年-

Developmental changes in galanin in lumbosacral sympathetic ganglionic neurons innervating the avian uterine oviduct and galanin induction by sex steroids.

T. Ubuka, H. Sakamoto, D. Li, K. Ukena and K. Tsutsui

J. Endocrinology170p.357 - 3682001年-

Developmental changes in progesterone biosynthesis and metabolism in the quail brain.

K. Ukena, Y. Honda, R. W. Lea and K. Tsutsui

Brain Res.898p.190 - 1942001年-

Distribution of novel RFamide-related peptide-like immunoreactivity in the mouse central nervous system.

K. Ukena and K. Tsutsui

Neurosci. Lett.300p.153 - 1562001年-

Effects of progesterone synthesized de novo in the developing Purkinje cell on its dendritic growth and synaptogenesis.

H. Sakamoto, K. Ukena and K. Tsutsui

J. Neuroscience21p.6221 - 62322001年-

Expression and localization of cytochrome P45017alpha-hydroxylase/c17,20lyase in the avian brain.

M. Matsunaga, K. Ukena and K. Tsutsui

Brain Res.899p.112 - 1222001年-

Review: Biosynthesis and biological actions of neurosteroids in brain neurons.

K. Tsutsui

Zool. Sci.18p.1043 - 10532001年-

Review: Changes in central steroid receptor expression, steroid synthesis, and dopaminergic activity related to the reproductive cycle of the ring dove.

R. W. Lea and K. Tsutsui

Micros. Res. Tech. (MRT)55p.12 - 262001年-

The Zoological Society Prize: Biosynthesis and biological actions of neurosteroids in the brain.

K. Tsutsui

Zool. Sci.18p.1 - 22001年-

Steroidogenesis in the avian brain.

K. Tsutsui and B. A. Schlinger

In: Avian Endocrinology,p.59 - 772001年-

Novel cerebellar function: Neurosteroids in the Purkinje neuron and their genomic and non-gemonic actions.

K. Tsutsui, K. Ukena and H. Sakamoto

In: Neural Plasticity, Development and Steroid Hormone Action,p.101 - 1192001年-

A novel hypothalamic peptide inhibiting gonadotropin release.

K. Tsutsui, K. Ukena, E. Saigoh, H. Teranishi, H. Satake, Y. Fujisawa, H. Minakata, M. Kikuchi, S. Ishii and P. J. Sahrap

In : Perspective in Comparative Endocrinology,p.481 - 4892001年-

A novel avian hypothalamic peptide.

K. Tsutsui, E. Saigoh, H. Teranishi, K. Ukena, Y. Fujisawa, M. Kikuchi, S. Ishii and P. J. Sharp

In: Recent Advances in Comparative Endocrinology,p.207 - 2142001年-

Isolation and characterization of a GnRH-like peptide from Octopus vulgaris.

E. Iwakoshi, K. Takuwa-Kuroda, Y. Fujisawa, M. Hisada, K. Ukena, K. Tsutsui and H. Minakata

In : Perspective in Comparative Endocrinology,p.585 - 5902001年-

Sympathetic ganglionic galanin neurons evoke avian oviposition by innervating the uterine oviduct: A novel neuronal mechanism of avian oviposition.

H. Sakamoto, T. Ubuka, C. Kohchi, K. Ukena and K. Tsutsui

In : Perspective in Comparative Endocrinology,p.647 - 6532001年-

Effects of progesterone synthesized de novo in the developing Purkinje cell on its dendritic growth and synaptogenesis

H. Sakamoto, K. Ukena and K. Tsutsui

J. Neuroscience21p.6221 - 62322001年-

Activity and localization of 3-hydroxysteroid dehydrogenase/5-4-isomerase in the zebrafish central nervous system

H. Sakamoto, K. Ukena and K. Tsutsui

J. Comp. Neurol.439p.291 - 3052001年-

Developmental changes in galanin in lumbosacral sympathetic ganglionic neurons innervating the avian uterine oviduct and galanin induction by sex steroids

T. Ubuka, H. Sakamoto, D. Li, K. Ukena and K. Tsutsui

J. Endocrinology170p.357 - 3682001年-

Developmental changes in progesterone biosynthesis and metabolism in the quail brain

K. Ukena, Y. Honda, R. W. Lea and K. Tsutsui

Brain Res.898p.190 - 1942001年-

Expression and localization of cytochrome P45017-hydroxylase/c17,20lyase in the avian brain

M. Matsunaga, K. Ukena and K. Tsutsui

Brain Res.899p.112 - 1222001年-

Distribution of novel RFamide-related peptide-like immunoreactivity in the mouse central nervous system

K. Ukena and K. Tsutsui

Neurosci. Lett.300p.153 - 1562001年-

Characterization of a cDNA encoding a novel avian hypothalamic neuropeptide exerting an inhibitory effect on gonadotropin release

H. Satake, M. Hisada, T. Kawada, H. Minakata, K. Ukena and K. Tsutsui

Biochemical J.354p.379 - 3852001年-

A novel hypothalamic neuropeptide: Gonadotropin-inhibitory hormone

K. Tsutsui, K. Ukena, E. Saigoh, H. Teranishi, Y. Fujisawa, H. Satake, H. Minakata and P. J. Sharp

Internat. J. Mol. Med.8p.400 - 4052001年-

A novel avian hypothalamic peptide inhibiting gonadotropin release.

K. Tsutsui, E. Saigoh, K. Ukena, H. Teranishi, Y. Fujisawa, M. Kikuchi, S. Ishii and P. J. Sharp

Biochem. Biophys. Res. Commun.275p.661 - 6672000年-

Avian galanin: Cloning of complementary DNAs and characterization of transcripts in different tissues.

C. Kohchi and K. Tsutsui

J. Exp. Zool.287p.183 - 1902000年-

Existence of galanin in lumbosacral sympathetic ganglionic neurons that project to the quail uterine oviduct.

H. Sakamoto, T. Ubuka, C. Kohchi, D. Li, K. Ukena and K. Tsutsui

Endocrinology141p.4402 - 44122000年-

Novel cerebellar function: Biosynthesis and actions of neurosteroids in the Purkinje neuron.

K. Tsutsui and K. Ukena

Internat. J. Mol. Med.6p.218 - 2212000年-

Review: Novel brain function: biosynthesis and actions of neurosteroids in neurons.

K. Tsutsui, K. Ukena, M. Usui, H. Sakamoto and M. Takase

Neurosci. Res.36p.261 - 2732000年-

Neuronal neurosteroidogenesis in the cerebellum.

K. Tsutsui and K. Ukena

In: Molecular Steroidogenesis,p.397 - 4002000年-

総説 : 小脳における神経ステロイドの合成と作用

筒井和義

「ステロイドホルモンと脳科学:性・ストレス・脳をめぐって」第14回「大学と科学」公開シンポジウム組織委員会編p.139 - 1462000年-

総説 : 小脳プルキンエ細胞におけるニューロステロイドの合成と作用

筒井和義

自律神経(自律神経学会編)37p.235 - 2432000年-

総説 : 神経ステロイドによるシナプス可塑性調節

筒井和義、浮穴和義、坂本浩隆

特集:脳のシナプス Brain Medical12p.298 - 3062000年-

Existence of galanin in lumbosacral sympathetic ganglionic neurons that project to the quail uterine oviduct

H. Sakamoto, T. Ubuka, C. Kohchi, D. Li, K. Ukena and K. Tsutsui

Endocrinology141p.4402 - 44122000年-

A novel avian hypothalamic peptide inhibiting gonadotropin release

K. Tsutsui, E. Saigoh, K. Ukena, H. Teranishi, Y. Fujisawa, M. Kikuchi, S. Ishii and P. J. Sharp

Biochem. Biophys. Res. Commun.275p.661 - 6672000年-

Novel cerebellar function: Biosynthesis and actions of neurosteroids in the Purkinje neuron

K. Tsutsui and K. Ukena

Internat. J. Mol. Med.6p.218 - 2212000年-

Avian galanin: Cloning of complementary DNAs and characterization of transcripts in different tissues

C. Kohchi and K. Tsutsui

J. Exp. Zool.287p.183 - 1902000年-

Expression and activity of 3beta-hydroxysteroid dehydrogenase/delta5-delta4-isomerase in the rat Purkinje neuron during neonatal life.

K. Ukena, C. Kohchi and K. Tsutsui

Endocrinology140(2)p.805 - 8131999年02月-1999年02月 

DOI

Biosynthesis and function of neurosteroids in vertebrate brains.

K. Tsutsui

Hormone Frontier in Gynecology6p.1 - 61999年-

Expression and activity of 3beta-hydroxysteroid dehydrogenase/D5-D4-isomerase in different regions of the avian brain.

K. Ukena, Y. Honda, Y. Inai, C. Kohchi, R. W. Lea and K. Tsutsui

Brain. Res.818p.536 - 5421999年-

Expression of steroidogenic enzymes and metabolism of steroids in COS-7 cells known as non-steroidogenic cells

Nozaki, Mitsuki; Haraguchi, Shogo; Miyazaki, Takuro; Shigeta, Daichi; Kano, Noriko; Lei, Xiao Feng; Kim-Kaneyama, Joo Ri; Minakata, Hiroyuki; Miyazaki, Akira; Tsutsui, Kazuyoshi

Scientific Reports8(1)2018年12月-2018年12月 

DOIScopus

詳細

概要:© 2018 The Author(s). The COS-7 (CV-1 in Origin with SV40 genes) cells are known as non-steroidogenic cells because they are derived from kidney cells and the kidney is defined as a non-steroidogenic organ. Therefore, COS-7 cells are used for transfection experiments to analyze the actions of functional molecules including steroids. However, a preliminary study suggested that COS-7 cells metabolize [ 3 H]testosterone to [ 3 H]androstenedione. These results suggest that COS-7 cells are able to metabolize steroids. Therefore, the present study investigated the expression of steroidogenic enzymes and the metabolism of steroids in COS-7 cells. RT-PCR analyses demonstrated the expressions of sev eral kinds of steroidogenic enzymes, such as cytochrome P450 side-chain cleavage enzyme, 3β-hydroxysteroid dehydrogenase/Δ 5 -Δ 4 isomerase, cytochrome P450 7α-hydroxylase, cytochrome P450 17α-hydroxylase/17,20-lyase, 17β-hydroxysteroid dehydrogenase, 5α-reductase, cytochrome P450 21-hydroxylase, cytochrome P450 11β-hydroxylase, and cytochrome P450 aromatase in COS-7 cells. In addition, steroidogenic enzymes 3β-HSD, P4507α, 5α-reductase, P450c17, P450c21, P450c11β, and 17β-HSD actively metabolized various steroids in cultured COS-7 cells. Finally, we demonstrated that 17β-HSD activity toward androstenedione formation was greater than other steroidogenic enzyme activities. Our results provide new evidence that COS-7 cells express a series of steroidogenic enzyme mRNAs and actively metabolize a variety of steroids.

書籍等出版物

The E-Book of Neurosteroids: Frontiers Research Topic

H. Vaudry, K. Tsutsui

Frontiers in Endocrinology2013年-

Neurosteroids and synaptic formation in the cerebellum. In: Handbook of Cerebellum and Cerebellar Disorders

K. Tsutsui

Springer2013年-

Gonadotropin-inhibitory hormone (GnIH). In: The Handbook of Biologically Active Peptides (2nd edition) Brain Peptides Section

K. Tsutsui and T. Ubuka

Elsevier publisher2012年-

26RFa. In: The Handbook of Biologically Active Peptides (2nd edition) Brain Peptides Section

J. Leprince, C. Neveu, B. Lefrance, L. Guilhaudis, I. Segalas-Milazzo, J.-C. Do Rego, M. Tena-Sempere, K. Tsutsui and H. Vaudry

Elsevier publisher2012年-

Neurosteroids and synaptic formation in the cerebellum. In: Handbook of Cerebellum and Cerebellar Disorders

K. Tsutsui

Springer2011年-

Melatonin action on neuropeptide induction through receptor-mediated mechanisms in the brain. In: Melatonin: From Molecules to Therapy

K. Tsutsui, T. Ubuka and G. E. Bentley

Nova Science Publishers, New York2007年-

Phylogenetic aspects of gonadotropin-inhibitory hormone (GnIH) and its homologs in vertebrates. In: Phylogenetic Aspects of Neuropeptides: From Invertebrates to Humans

K. Tsutsui

Blackwell, Boston, Massachusetts2010年-

Gonadotropin-inhibitory hormone (GnIH) in the avian brain. In: Hormone Biotechnology

K. Tsutsui

Daya Publishing House, Delhi2007年-

Neuronal neurosteroidogenesis and organizing actions of neurosteroids during cerebellar development. In: Evolutionary Molecular Strategies and Plasticity

K. Tsutsui

Research Signpost Publishers, Trivandrum2007年-

ホルモンハンドブック 新訂eBook版 日本比較内分泌学会編

筒井和義

南江堂2007年-

脳ホルモンの新領域 シリーズ21世紀の動物科学 10 内分泌と生命現象

筒井和義, 浮穴和義, 南方宏之

培風館2007年-

Endocrinology of reproduction. In: Reproductive Biology and Phylogeny of Birds

G. E. Bentley, K. Tsutsui and J. C. Wingfield

Science Publishers, Enfield2006年-

Avian gonadotropin-inhibitory hormone (GnIH): Identification, mode of action and functional significance. In: Comparative Endocrinology and Biodiversity in Asia and Oceania

K. Tsutsui

Chulalongkorn University Press, Bangkok2006年-

Melatonin action on the induction of gonadotropin-inhibitory hormone in the avian brain. In: Comparative Endocrinology and Biodiversity in Asia and Oceania

V. S. Chowdhury, T. Ubuka, G. E. Bentley, K. Ukena, J. C. Wingfield and K. Tsutsui

Chulalongkorn University Press, Bangkok2006年-

The RFamide-related peptides. In: The Handbook of Biologically Active Peptides

N. Chartrel, K. Tsutsui, J. Costentin and H. Vaudry

Elsevier publisher2006年-

Structure, action and functional significance of GnIH. In: Functional Avian Endocrinology

K Tsutsui, G Bentley and N Ciccone

Narosa Publishing House, New Delhi2005年-

Classical and novel neurosteroids in vertebrate brains. In: Trends in Comparative Endocrinology

K. Tsutsui, M. Matsunaga, H. Miyabara, K. Ukena

AOSCE2004年-

A novel amphibian neurosteroid stimulating locomotor activity. In: Trends in Comparative Endocrinology

M. Matsunaga, K. Ukena, K. Tsutsui

AOSCE2004年-

Novel avian neurosteroid: Identification of 7alpha-hydroxypregnenolone in the quail brain. In: Trends in Comparative Endocrinology

H. Miyabara, M. Matsunaga, K. Ukena, K. Tsutsui

AOSCE2004年-

Synapse formation in response to estrogen synthesized de novo in the developing Purkinje cell. In: Trends in Comparative Endocrinology

H. Shikimi, H. Sakamoto, K. Ukena and K. Tsutsui

AOSCE2004年-

Immunohistochemical localization of the neuropeptides in the paraventricular organ of the Japanese grass lizard, Takydromus tachydromoides. In: Trends in Comparative Endocrinology

E. Kawano, T. Oishi, K. Ukena, K. Tsutsui and S. Tamotsu

AOSCE2004年-

Comparative aspects of novel hypothalamic LPXRF-amide peptides in the vertebrate brain: Structure, localization and function. In: Trends in Comparative Endocrinology

K. Ukena, K. Sawada, A. Kod, K. Yamamoto, S. Kikuyama, H. Satake, E. Iwakoshi-Ukena, H. Minakata, K. Tsutsui

AOSCE2004年-

Identification and localization of a novel lamprey hypothalamic neuropeptide of the RF-amide peptide family. In: Trends in Comparative Endocrinology

T. Osugi, K. Ukena, M. Nozaki, H. Kawauchi, S. A. Sower and K. Tsutsui

AOSCE2004年-

Effects of RF-amide peptides on the release of TSH from the bullfrog pituitary. In: Trends in Comparative Endocrinology

K. Yamamoto, A. Koda, K. Ukena, R. Okada, E. Iwakoshi-Ukena, H. Minakata, K. Tsutsui and S. Kikuyama

AOSCE2004年-

Trends in Comparative Endocrinology.

T. Oishi, K. Tsutsui, S. Tanaka and S. Kikuyama

AOSCE2004年-

Steroidogenesis in the avian brain. In: Avian Endocrinology

K. Tsutsui and B. A. Schlinger

Journal of Endocrinology Ltd2001年-

Novel cerebellar function: Neurosteroids in the Purkinje neuron and their genomic and non-gemonic actions. In: Neural Plasticity, Development and Steroid Hormone Action

K. Tsutsui, K. Ukena and H. Sakamoto

CRC Press, Florida2001年-

A novel hypothalamic peptide inhibiting gonadotropin release. In : Perspective in Comparative Endocrinology

K. Tsutsui, K. Ukena, E. Saigoh, H. Teranishi, H. Satake, Y. Fujisawa, H. Minakata, M. Kikuchi, S. Ishii and P. J. Sharp

Monduzzi Editore, Bologna2001年-

A novel avian hypothalamic peptide. In: Recent Advances in Comparative Endocrinology

K. Tsutsui, E. Saigoh, H. Teranishi, K. Ukena, Y. Fujisawa, M. Kikuchi, S. Ishii and P. J. Sharp

Academia Sinica, Taipei2001年-

Isolation and characterization of a GnRH-like peptide from Octopus vulgaris. In : Perspective in Comparative Endocrinology

E. Iwakoshi, K. Takuwa-Kuroda, Y. Fujisawa, M. Hisada, K. Ukena, K. Tsutsui and H. Minakata

Monduzzi Editore, Bologna2001年-

Sympathetic ganglionic galanin neurons evoke avian oviposition by innervating the uterine oviduct: A novel neuronal mechanism of avian oviposition. In : Perspective in Comparative Endocrinology

H. Sakamoto, T. Ubuka, C. Kohchi, K. Ukena and K. Tsutsui

Monduzzi Editore, Bologna2001年-

Neuronal neurosteroidogenesis in the cerebellum. In: Molecular Steroidogenesis

K. Tsutsui and K. Ukena

Universal Academy Press, Tokyo2000年-

講演・口頭発表等

Kiss2の分子進化に関する研究

日本動物学会 第84回 岡山大会 20132013年09月27日

詳細

口頭発表(一般)

生殖生理と生殖行動を変化させる社会的刺激の脳内機構

日本動物学会 第84回 岡山大会 20132013年09月26日

詳細

口頭発表(一般)

GnIH はニューロエストロゲン合成を促進して攻撃行動を抑制する

日本動物学会 第84回 岡山大会 20132013年09月26日

詳細

口頭発表(一般)

GnIHによるGnRHニューロン内シグナリング抑制機構

日本動物学会 第84回 岡山大会 20132013年09月26日

詳細

口頭発表(一般)

松果体で合成されたアロプレグナノロンは小脳プルキンエ細胞の細胞死を防ぐ

日本動物学会 第84回 岡山大会 20132013年09月26日

詳細

口頭発表(一般)

サケの遡上行動を促進する7alpha-ヒドロキシプレグネノロンの作用機構

日本動物学会 第84回 岡山大会 20132013年09月26日

詳細

口頭発表(一般)

GnIHによる視床下部P450arom活性の制御と性差

平成22年度〜平成26年度 文部科学省科学研究費補助金 新学術領域研究「性差構築の分子基盤」第5回領域会議2013年09月06日

詳細

口頭発表(一般)

-

2013年07月18日

詳細

口頭発表(一般)

-

2013年07月18日

詳細

口頭発表(一般)

-

2013年07月18日

詳細

口頭発表(一般)

-

2013年07月16日

詳細

口頭発表(一般)

-

2013年07月16日

詳細

口頭発表(一般)

発達期の小脳におけるニューロステロイドの生合成とオーガナイジング作用

第85回日本生化学会大会2012年12月14日

詳細

口頭発表(一般)

性腺機能を抑制する新規脳ホルモン、生殖腺刺激ホルモン放出抑制ホルモン(GnIH)の作用機構と発現制御機構

第35回日本分子生物学会2012年12月11日

詳細

口頭発表(一般)

ニューロンが合成するニューロステロイドの オーガナイジング作用

第28回小児成長研究会2012年07月28日

詳細

口頭発表(一般)

生殖を制御する新規脳ホルモンの 作用機構と発現制御機構

2012年07月14日

詳細

口頭発表(一般)

性腺機能を調節するGnIHの作用機構と発現制御機構

第84回日本内分泌学会学術総会2012年04月21日

詳細

口頭発表(一般)

特許

整理番号:865

新規メタスチン同族体およびその用途(日本)

筒井 和義, 大杉 知裕, 恒川 賢太

特願2008-253859、特開2010- 83793

外部研究資金

科学研究費採択状況

研究種別:

温帯性多回産卵魚のモデル生物・マミチョグを用いた水温刺激による成熟促進反応の解析

2013年-0月-2016年-0月

配分額:¥5200000

研究種別:

ヒト疾患解析にもとづく性差構築機序の解明

2010年-0月-2015年-0月

配分額:¥181740000

研究種別:

生殖制御における新規脳内分子機構の解明

2010年-0月-2015年-0月

配分額:¥217620000

研究種別:

新規脳分子による新しい生殖制御機構の解明

配分額:¥107770000

研究種別:

ストレスと社会適応

配分額:¥3200000

研究種別:

ニューロステロイドによる脳の性分化メカニズム

配分額:¥84000000

研究種別:

性分化機構

配分額:¥49700000

研究種別:

新規視床下部ホルモンによる脳下垂体ホルモン合成・放出の新しい制御機構

配分額:¥40040000

研究種別:

脂溶性シグナル分子の脳機能に対する作用機構

配分額:¥3300000

研究種別:

小脳プルキンエ細胞のニューロステロイドが導くシナプス形成とシナプス機能発達

配分額:¥4200000

研究種別:基盤研究(C)

学習の生物学的基盤に関する総合的研究

2000年-2000年

研究分野:動物生理・代謝

配分額:¥3400000

研究種別:

新規脳分子であるニューロステロイドによる本能行動のモティベーション制御

配分額:¥14900000

研究種別:

頭足類マダコの循環および生殖系に作用する神経ペプチドの生理・生化学的研究

配分額:¥3700000

研究種別:

神経ステロイドによる海馬での情動記憶交信の活性化

配分額:¥15500000

研究種別:

プルキンエ細胞が合成するニューロステロイドによる小脳神経回路形成と運動学習制御

配分額:¥6500000

研究種別:

新しい脳ペプチド分離の新戦略

配分額:¥37350000

研究種別:

記憶ニューロンが合成するニューロステロイドによるシナプス活動制御と運動学習の解析

配分額:¥2200000

研究種別:

ウズラ雛「刷り込み」学習の遺伝的・神経的基盤

配分額:¥4700000

研究種別:基盤研究(B)

脳内ニューロステロイドの生合成制御機構と作用機構に関する研究

1996年-1997年

研究分野:植物形態・構造

配分額:¥7600000

研究種別:基盤研究(B)

マルチペプチド合成機による神経ペプチドアンタゴニストの開発とその応用

1996年-1997年

研究分野:動物生理・代謝

配分額:¥5200000

研究種別:一般研究(C)

行動の調節因子として働くステロイドホルモンの神経細胞内作用機序

1993年-1994年

研究分野:生物形態・構造

配分額:¥2100000

研究種別:一般研究(B)

生殖機能の経時的変化における神経内分泌調節

1987年-1988年

研究分野:動物形態・分類学

配分額:¥6500000

研究種別:一般研究(A)

哺乳類生殖内分泌系の成熟とエイジングの機構

1984年-1986年

研究分野:動物形態・分類学

配分額:¥15500000

研究種別:

甲状腺ホルモンによる生殖制御におけるGnIHシステムの作用機構

2015年-0月-2017年-0月

配分額:¥2300000

研究種別:

「性差構築の分子基盤」の領域運営と支援活動

2010年-0月-2015年-0月

配分額:¥37830000

研究資金の受入れ状況

実施形態:共同研究

日仏(JSPS-INSERM)国際共同研究「ストレスによるニューロステロイド合成の変動とその制御機構」2008年-2009年

実施形態:共同研究

日本学術振興会外国人招聘研究者(短期)「鳥類におけるストレスホルモン応答の違いを規定する脳遺伝子の同定」2008年-

実施形態:共同研究

広島大学総合脳科学研究プロジェクト「本能と記憶・学習の脳制御システムの多角的解析」1996年-2006年

実施形態:共同研究

米(NIH)日国際共同研究「新規脳ペプチドの探索とその機能解析に関する研究」2002年-2004年

実施形態:その他

内分泌かく乱物質とニューロステロイド作用2000年-2002年

実施形態:共同研究

ニューロステロイドに関するヒューマンフロンティアサイエンス2000年-2002年

実施形態:共同研究

英日国際共同研究「ニューロステロイドの合成と作用に関するプレインサイエンス」1997年-2001年

実施形態:共同研究

本能と記憶・学習の脳制御システムの多角的解析1996年-2006年

学内研究制度

特定課題研究

新たに発見された松果体ニューロステロイドの生合成制御機構と作用機構の解明

2016年度

研究成果概要:Biosynthesis and mode of action of pineal neurosteroidsKazuyoshi TsutsuiWe have discovered that the pineal gland ac...Biosynthesis and mode of action of pineal neurosteroidsKazuyoshi TsutsuiWe have discovered that the pineal gland actively produces a variety of neurosteroids, such as. 7α-hydroxypregnenolone and allopregnanolone. We have further demonstrated that 7α-hydroxypregnenolone stimulates locomotor activity and allopregnanolone saves cerebellar Purkinje cells.

社会環境による生殖行動変容の脳内分子機構の解明

2015年度

研究成果概要:社会環境の変化によって動物の行動や生殖腺から分泌される性ホルモンの血中濃度が変化することはこれまでに多くの研究者が報告してきました。社会環境の変化というのは、動物が一匹でいる状態からつがいになる、群れで生活していたのにはぐれてしま...社会環境の変化によって動物の行動や生殖腺から分泌される性ホルモンの血中濃度が変化することはこれまでに多くの研究者が報告してきました。社会環境の変化というのは、動物が一匹でいる状態からつがいになる、群れで生活していたのにはぐれてしまって一匹になるといった個体をとりまく環境の変化です。社会環境の変化は、視覚や聴覚などの感覚系で受容された後、脳に変化をもたらして動物の生理状態や行動を調節します。人間も社会的な情報によって行動や生理状態は瞬時に変化します。例えば、異性と同性の前では態度や行動が変わってしまうことや、素敵な異性を前にすると性ホルモンの分泌が変化するということは一般的に言われています。しかしながら、それらがどのような機構によって発現されるのかは不明のままでした。本研究により、異性の存在が、ノルエピネフリンやGnIHを介して、性ホルモンの分泌を瞬時に変化させる新しい神経機構が解明されました。本研究成果は、雌の存在を認知する際に視覚に大きく依存する動物モデルとして、鳥類のウズラから得られたものですが、ノルエピネフリンやGnIHなどの脳ホルモンが多くの動物に共通して存在することから、私たちヒトを含めた哺乳類でも社会的な情報が生理状態を変化させるうえで、同じ仕組みが存在するかもしれません。よって将来的にヒトが一目ぼれするときの神経機構や分子メカニズムの解明に貢献することが期待されます。

脳の性的可逆性と不可逆性の分子基盤

2015年度

研究成果概要:生殖腺に精巣と卵巣があるように、脳にも雄型と雌型があり、その違いによって、種々の行動に性差がもたらされる。哺乳類や鳥類では、出生前後の一時期に脳が雄型か雌型のどちらかに分化を遂げ、通常、そこで決まった脳の性は固定化されて生涯逆転す...生殖腺に精巣と卵巣があるように、脳にも雄型と雌型があり、その違いによって、種々の行動に性差がもたらされる。哺乳類や鳥類では、出生前後の一時期に脳が雄型か雌型のどちらかに分化を遂げ、通常、そこで決まった脳の性は固定化されて生涯逆転することはない。一方、魚類の脳は、生涯にわたって性的な可逆性が保持される。このように、脳の性の固定化と可逆性は動物種によって大きく異なるが、その分子機構は未解明である。本研究は、脳の性の揺らぎを抑制する分子基盤を得るために、脳の性の固定化が強いウズラを研究対象にし、脳の性の固定化を規定する分子機構と顕著な性差が認められる生殖行動、攻撃行動、自発運動の性依存的行動パターンが固定化される機構を明らかにすることを目的とした。本研究により、ウズラにおいて、生殖行動、攻撃行動、自発運動は脳内のステロイド(エストロゲンおよび7α-水酸化プレグネノロン)合成系・作用系により制御され、この制御機構には著しい性差があり、生活史の早い段階の一時期に形成され、一生涯にわたって維持されることを見出した。

生殖制御の新しい分子ネットワークの実体とその変容・破綻機構の解明

2017年度

研究成果概要:Title : Novel molecular networks regulating reproduction: Discovery, changes and regulationKazuyoshi TsutsuiGonadot...Title : Novel molecular networks regulating reproduction: Discovery, changes and regulationKazuyoshi TsutsuiGonadotropin-inhibitory hormone (GnIH) is a newly discovered neuropeptide inhibiting gonadotropin secretion. This study demonstrated that GnIH regulates reproduction in vertebrates including human. This study further demonstrated that GnIH is involved in pubertal disorder. 

現在担当している科目

科目名開講学部・研究科開講年度学期
動物の機能II(ホルモンによる調節)教育学部2019秋学期
脳科学I教育学部2019春学期
脳科学II教育学部2019秋学期
動物形態学・実験教育学部2019秋学期
生物学演習教育学部2019通年
生物学実験II教育学部2019通年
生物学特殊演習 G教育学部2019通年
修士論文(生命理工)大学院先進理工学研究科2019通年
Research on Integrative Brain Sciences大学院先進理工学研究科2019通年
統合脳科学研究大学院先進理工学研究科2019通年
Integrative Bioscience and Biomedical Engineering B大学院先進理工学研究科2019秋学期
総合生命理工学特論B大学院先進理工学研究科2019秋学期
Seminar on Integrative Brain Sciences A大学院先進理工学研究科2019春学期
統合脳科学演習A大学院先進理工学研究科2019春学期
Seminar on Integrative Brain Sciences B大学院先進理工学研究科2019秋学期
統合脳科学演習B大学院先進理工学研究科2019秋学期
Seminar on Integrative Brain Sciences C大学院先進理工学研究科2019春学期
統合脳科学演習C大学院先進理工学研究科2019春学期
Seminar on Integrative Brain Sciences D大学院先進理工学研究科2019秋学期
統合脳科学演習D大学院先進理工学研究科2019秋学期
Master's Thesis (Department of Integrative Bioscience and Biomedical Engineering)大学院先進理工学研究科2019通年
統合脳科学研究大学院先進理工学研究科2019通年

作成した教科書・教材・参考書

高等学校「生物」第一学習社 監修

2013年

高等学校「新生物基礎」第一学習社 監修

2012年

高等学校「生物基礎」 第一学習社 監修

2012年