生殖制御における新規脳内分子機構の解明

2013 Fiscal Year Annual Research Report

• Project/Area Number: 22227002
• Research Institution: Waseda University
• Principal Investigator: 筒井 和義 早稲田大学, 教育・総合科学学術院, 教授 (20163842)
• Co-Investigator(Kenkyū-buntansha): 緒方 勤 浜松医科大学, 医学部, 教授 (40169173)
• Project Period (FY): 2010-05-31 – 2015-03-31
• Keywords: 視床下部ホルモン / 脳下垂体ホルモン / 発現制御 / シグナル伝達 / 生殖 / 生殖行動 / 生殖機能異常 / 分子進化

Research Abstract

「GnIH生殖抑制作用の分子機構の解析」：GnIHの標的細胞であるGnRHニューロン（細胞株GT1-7）においてGnIHはcAMP合成を低下させてERKのリン酸化を阻害することを明らかにした。GnIHの標的細胞であるキスペプチンニューロン（細胞株rHypoE22）におけるGnIH作用の分子機構を解析した。 「GnIH発現の分子制御機構の解析」：GnIHの発現は光周期がメラトニンや甲状腺ホルモンを介して、ストレスがグルココルチコイドを介して、社会環境がノルエピネフリンを介して変動させることを明らかにした。 「生殖腺におけるGnIHの局所作用機構の解析」：卵巣の顆粒膜細胞と精巣の間質細胞に発現するGnIHの局所作用により性ステロイド合成酵素の発現と性ステロイドの合成が低下することを明らかにした。 「GnIHによる生殖行動の発現制御機構の解析」：GnIHが脳内P450aromの活性を高めてエストロゲン合成を増加させ、生殖行動の発現を抑制することを明らかにした。 「GnIH遺伝子のノックダウンとノックアウトによるGnIH生理作用の解析」：GnIH遺伝子のノックダウン（ウズラ）により、GnIHは生殖と生殖行動を抑制することを明らかにした。GnIH遺伝子のノックアウト（マウス）により、GnIHの生理作用を解析した。 「GnIHによるヒト生殖機能異常の分子機構の解析」：中枢性生殖機能異常症患者のDNA検体を継続して集積し、次世代シーケンサーによりGnIH遺伝子とGnIH受容体遺伝子の変異解析を進めた。 「動物界におけるGnIHとGnIH受容体の起源と分子進化の解析」：GnIHとGnIH受容体は脊椎動物のみならず、原索動物（ナメクジウオ）に存在することを明らかにした。これまでに同定した全ての遺伝子のシンテニー解析を行い、GnIHとGnIH受容体の起源と分子進化を解析した。

Current Status of Research Progress

1: Research has progressed more than it was originally planned.

Reason

事前の十分な準備と適切な研究計画により、当初の目的を超える研究の進展があり、本年度に受けた当該研究の研究進捗状況の評価はA+であった。GnIH生殖抑制作用の分子機構、GnIH発現の分子制御機構、生殖腺におけるGnIHの局所作用機構、GnIHによる生殖行動の発現制御機構などに重要な新知見が数多く得られた。また、GnIH遺伝子のノックダウンによりGnIHの生殖と生殖行動の抑制作用が証明された。さらに、GnIH とGnIH受容体は脊椎動物のみならず、原索動物（ナメクジウオ）に存在することが明らかとなり、動物界におけるGnIHとGnIH受容体の起源と分子進化に重要な知見が得られた。このような予想以上の研究進展により、古典的な理解とは遥かにかけ離れた「生殖制御における新規脳内分子機構」の理解が著しく進展した。

Strategy for Future Research Activity

今後の研究では、継続して生化学的手法と分子生物学的手法を用いてGnIH生殖抑制作用の分子機構、GnIH発現の分子制御機構、生殖腺におけるGnIHの局所作用機構、GnIHによる生殖行動の発現制御機構をさらに詳しく解析する。また、GnIH遺伝子のノックアウトマウスの作製に成功したので、中枢性思春期早発や中枢性生殖機能異常に着目したGnIH作用の生理的意義を解析する。さらに、GnIH遺伝子のノックアウトマウスを用いてGnIHの新しい生理作用を解析する。加えて、中枢性生殖機能異常症患者のDNA検体が集積したので、次世代シーケンサーを用いて本格的にGnIH遺伝子とGnIH受容体遺伝子の変異解析を進める。一方、GnIHとGnIH受容体の起源は原索動物（ナメクジウオ）に遡ることを明らかにしたので、他の無脊椎動物からGnIHとGnIH受容体を同定し、遺伝子のシンテニー解析を行う。全ての研究準備を終えており、今後の研究推進に問題は無い。予想を上回る研究の成果が見込まれる。

Research Products

• [Journal Article] 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 (2014)
  • Author(s): M. R. J. Shirazi, M. J. Zamiri, M. S. Salehi, S. Moradi, A. Tamadon, M. R. Namavar, A. Akhlaghi, K. Tsutsui, A. Caraty
  • Journal Title: J. Neuroendocrinol. Volume: 印刷中 Pages: in press
  • DOI: 10.1111/jne12137
  • Peer Reviewed
• [Journal Article] Molecular basis for the activation of gonadotropin-inhibitory hormone gene transcription by corticosterone (2014)
  • Author(s): Y. L. Son, T. Ubuka, M. Narihiro, Y. Fukuda, I. Hasunuma, K. Yamamoto, D. D. Belsham, K. Tsutsui
  • Journal Title: Endocrinology Volume: 印刷中 Pages: in press
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  • Peer Reviewed
• [Journal Article] Hypothalamic inhibition of socio-sexual behaviour by increasing neuroestrogen synthesis (2014)
  • Author(s): T. Ubuka, S. Haraguchi, Y. Tobari, M. Narihiro, K. Ishikawa, T. Hayashi, N. Harada, K. Tsutsui
  • Journal Title: Nat. Commun. Volume: 5 Pages: 3061
  • DOI: 10.1038/ncomms4061
  • Peer Reviewed
• [Journal Article] Review: Breakthrough in neuroendocrinology by discovering novel neuropeptides and neurosteroids: 1) Discovery of gonadotropin-inhibitory hormone (GnIH) across vertebrates (2014)
  • Author(s): K. Tsutsui, T. Ubuka
  • Journal Title: Gen. Comp. Endocrinol. Volume: 印刷中 Pages: in press
  • DOI: 10.1016/j.ygcen.2014.03.006
  • Peer Reviewed
• [Journal Article] Review: Breakthrough in neuroendocrinology by discovering novel neuropeptides and neurosteroids: 2) Discovery of neurosteroids and pineal neurosteroids (2014)
  • Author(s): K. Tsutsui, S. Haraguchi
  • Journal Title: Gen. Comp. Endocrinol. Volume: 印刷中 Pages: in press
  • DOI: 10.1016/j.ygcen.2014.03.008
  • Peer Reviewed
• [Journal Article] Review: Gonadotropin-inhibitory hormone inhibits aggressive behavior of male quail by increasing neuroestrogen synthesis in the brain beyond its optimum concentration (2014)
  • Author(s): T. Ubuka, K. Tsutsui
  • Journal Title: Gen. Comp. Endocrinol. Volume: 印刷中 Pages: in press
  • DOI: 10.1016/j.ygcen.2014.03.014
  • Peer Reviewed
• [Journal Article] Review: Biosynthesis and biological action of pineal allopregnanolone (2014)
  • Author(s): K. Tsutsui, S. Haraguchi
  • Journal Title: Front. Neurosci. Volume: 印刷中 Pages: in press
  • DOI: 10.3389/fncel.2014.00118
  • Peer Reviewed
• [Journal Article] Review: Molecular evolution and function of 26RFa/QRFP and its cognate receptor (2014)
  • Author(s): K. Ukena, T. Osugi, J. Leprince, H. Vaudry, K. Tsutsui
  • Journal Title: J. Mol. Endocrinol. Volume: 印刷中 Pages: in press
  • DOI: 0.1530/JME-13-0207
  • Peer Reviewed
• [Journal Article] Review: Central and direct regulation of testicular activity by gonadotropin-inhibitory hormone and its receptor (2014)
  • Author(s): T. Ubuka, Y. L. Son, Y. Tobari, M. Narihiro, G. E. Bentley, L. Kriegsfeld, K. Tsutsui
  • Journal Title: Front. Endocrinol. (Lausanne) Volume: 5 Pages: 1-10
  • DOI: 10.3389/fendo.2014.00008
  • Peer Reviewed
• [Journal Article] 総説：化学掲示板‐女性ホルモンの量がオスの攻撃性を調整していた！（1月18日日本経済新聞掲載）筒井和義教授（早稲田大学教育・総合科学学術院／先端生命医科学センター）に聞く (2014)
  • Author(s): 筒井和義
  • Journal Title: 化学 Volume: 69 Pages: 73
  • Peer Reviewed
• [Journal Article] Uniparental disomy of chromosome 8 leading to homozygosity of a CYP11B1 mutation in a patient with congenital adrenal hyperplasia: Implication for a rare etiology of an autosomal recessive disorder (2014)
  • Author(s): K. Matsubara, N. Kataoka, S. Ogita, S. Sano, T. Ogata, M. Fukami, N. Katsumata
  • Journal Title: Endocr. J. Volume: 印刷中 Pages: in press
  • Peer Reviewed
• [Journal Article] Lack of genomic rearrangements involving the aromatase gene CYP19A1 in breast cancer (2014)
  • Author(s): M. Fukami, J. Suzuki, K. Nakabayashi, R. Tsunashima, T. Ogata, M. Shozu, S. Noguchi
  • Journal Title: Breast Cancer Volume: 印刷中 Pages: in press
  • Peer Reviewed
• [Journal Article] TBX1 Mutation identified by exome sequencing in a Japanese family with 22q11.2 deletion syndrome-like craniofacial features and hypocalcemia (2014)
  • Author(s): T. Ogata, T. Niihori, N. Tanaka, M. Kawai, T. Nagashima, R. Funayama, K. Nakayama, S. Nakashim, F. Kato, M. Fukami, Y. Aoki, Y. Matsubara
  • Journal Title: PLoS. One Volume: 9 Pages: e9158
  • DOI: 10.1371/journal.pone.0091598
  • Peer Reviewed
• [Journal Article] Identification and functional characterization of two novel NPR2 mutations in Japanese patients with short stature (2014)
  • Author(s): N. Amano, T. Mukai, Y. Ito, S. Narumi, T. Tanaka, S. Yokoya, T. Ogata, T. Hasegawa
  • Journal Title: J. Clin. Endocrinol. Metab. Volume: 99 Pages: E713-E718
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  • Peer Reviewed
• [Journal Article] Genome-wide parent-of-origin DNA methylation analysis reveals the intricacies of the human imprintome and suggests a germline methylation independent establishment of imprinting (2014)
  • Author(s): F. Court, C. Tayama, V. Romanelli, A. Martin-Trujillo, I. Iglesias-Platas, K. Okamura, N. Sugahara, C. Simon, H. Moore, J. Harness, H. Keirstead, J. V. Sanchez-Mut, E. Kaneki, P. Lapunzina, H. Soejima, N. Wake, M. Esteller, T. Ogata, K. Hata, K. Nakabayashi, D. Monk
  • Journal Title: Genome Res. Volume: 24 Pages: 54-569
  • DOI: 10.1101/gr.164913.113
  • Peer Reviewed
• [Journal Article] Rationale and study design of the Japan environment and children’s study (JECS) (2014)
  • Author(s): T. Kawamoto, H. Nitta, K. Murata, E. Toda, N. Tsukamoto, M. Hasegawa, Z. Yamagata, F. Kayama, R. Kshi, Y. Ohya, H. Saito, H. Sago, M. Okuyama, T. Ogata, S. Yokoya, Y. Koresawa, Y. Shibata, S. Nakayama, T. Michikawa, A. Takeuchi, H. Saitoh
  • Journal Title: BMC. Public Health Volume: 印刷中 Pages: in press
  • DOI: 10.1186/1471-2458-14-25
  • Peer Reviewed
• [Journal Article] IMAGe syndrome: clinical and genetic implications based on investigations in three Japanese patients (2014)
  • Author(s): F. Kato, T. Hamajima, T. Hasegawa, N. Amano, R. Horikawa, G. Nishimura, S. Nakashima, T. Fuke, S. Sano, M. Fukami, T. Ogata
  • Journal Title: Clin. Endocrinol. Volume: 80 Pages: 706-713
  • DOI: 10.1111/cen.12379
  • Peer Reviewed
• [Journal Article] Disorder of sex development in an infant with molecularly confirmed 46,XY, +der(10)t(10;21)(q21.1;q21.3),-21, (2014)
  • Author(s): H. Yagasaki, T. Nakane, T. Saito, K. Koizumi, K. Kobayashi, T. Ogata
  • Journal Title: Am. J. Med. Genet. A Volume: 164A Pages: 841-843
  • DOI: 10.1002/ajmg.a.36354
  • Peer Reviewed
• [Journal Article] Prenatal Genetic testing for a microdeletion at chromosome 14q32.2 imprinted region leading to upd(14)pat-like phenotype (2014)
  • Author(s): A. Sasaki, M. Sumie, S. Eada, R. Kosaki, K. Kurosawa, M. Fukami, H. Sago, T. Ogata, M. Kagami
  • Journal Title: Am. J. Med. Genet. A Volume: 164A Pages: 264-266
  • DOI: 10.1002/ajmg.a.36185
  • Peer Reviewed
• [Journal Article] Compound heterozygous deletions in pseudoautosomal region 1 in an infant with mild manifestsations of Langer mesomelic dysplasia (2014)
  • Author(s): T. Tsuchiya, M. Shibata, H. Numabe, T. Jinnno, K. Nakabayashi, G. Nishimura, T. Nagai, T. Ogata, M. Fukami
  • Journal Title: Am. J. Med. Genet. A Volume: 164A Pages: 505-510
  • DOI: 10.1002/ajmg.a.36284
  • Peer Reviewed
• [Journal Article] Long term follow up study for a patient with Floating-Harbor syndrome due to a hotspot SRCAP mutation (2014)
  • Author(s): K. Nagasaki, T. Asami, H. Sato, Y. Ogawa, T. Kikuchi, A. Saitoh, T. Ogata, M. Fukami
  • Journal Title: Am. J. Med. Genet. A Volume: 164A Pages: 731-735
  • DOI: 10.1002/ajmg.a.36314
  • Peer Reviewed
• [Journal Article] Hypertrophic cells in hypophagic intrauterine growth retarded rats without catch-up growth (2014)
  • Author(s): K. Kitsuda, R. Yamaguchi, E. Nagata, Y. Nakagawa, T. Ohzeki, T. Ogata, T. Nakanishi
  • Journal Title: Kitasato Med. J. Volume: 44 Pages: 38-46
  • Peer Reviewed
• [Journal Article] Review: Aromatase excess syndrome: a rare autosomal dominant disorder leading to pre- or peri-pubertal onset gynecomastia (2014)
  • Author(s): M. Fukami, M. Miyado, K. Nagasaki, M. Shozu, T. Ogata
  • Journal Title: Pediatr. Endocr. Rev. Volume: 11 Pages: 298-305
  • Peer Reviewed
• [Journal Article] Contribution of de novo synthesis of Galphas-proteins to 1-methyladenine production in starfish ovarian follicle cells stimulated by relaxin-like gonad-stimulating substance (2013)
  • Author(s): M. Mita, S. Haraguchi, H. Uzawa, K. Tsutsui
  • Journal Title: Biochem. Biophys. Res. Commun. Volume: 440 Pages: 798-801
  • DOI: 10.1016/j.bbrc.2013.10.038
  • Peer Reviewed
• [Journal Article] Molecular evolution of Kiss2 genes and peptides in vertebrates (2013)
  • Author(s): T. Osugi, N. Ohtaki, Y. Sunakawa, Y. L. Son, M. Ohkubo, M. Iigo, M. Amano, K. Tsutsui
  • Journal Title: Endocrinology Volume: 154 Pages: 4270-4280
  • DOI: 10.1210/en.2012-2267
  • Peer Reviewed
• [Journal Article] Gonadotropin-inhibitory hormone reduces sexual motivation but not lordosis behavior in female Syrian hamsters (Mesocricetus auratus) (2013)
  • Author(s): D. J. Piekarski, S. Zhao, K. J. Jennings, T. Iwasa, S. J. Legan, J. D. Mikkelsen, K. Tsutsui, L. J. Kriegsfeld
  • Journal Title: Horm. Behav. Volume: 64 Pages: 501-510
  • DOI: 10.1016/j.yhbeh.2013.06.006
  • Peer Reviewed
• [Journal Article] A genetically female brain is required for a regular reproductive cycle in chicken brain chimeras (2013)
  • Author(s): 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, H. Ohki-Hamazaki
  • Journal Title: Nat. Commun. Volume: 4 Pages: 1372
  • DOI: 10.1038/ncomms2372
  • Peer Reviewed
• [Journal Article] Contribution of Leydig and Sertoli cells to testosterone production in mouse fetal testes (2013)
  • Author(s): Y. Shima, K. Miyabayashi, S. Haraguchi, T. Arakawa, H, Otake, T. Baba, S. Matsuzaki, Y. Shishido, H. Akiyama, T. Tachibana, K. Tsutsui, K. Morohashi
  • Journal Title: Mol. Endocrinol. Volume: 27 Pages: 63-73
  • DOI: 10.1210/me.2012-1256
  • Peer Reviewed
• [Journal Article] Review: Biosynthesis and biological actions of pineal neurosteroids in domestic birds, [Selected for Issue Cover] (2013)
  • Author(s): K. Tsutsui, S. Haraguchi, M. Hatori, T. Hirota, Y. Fukada
  • Journal Title: Neuroendocrinology Volume: 98 Pages: 97-105
  • DOI: 10.1159/000353782
  • Peer Reviewed
• [Journal Article] Review: New biosynthesis and biological actions of avian neurosteroids (2013)
  • Author(s): K. Tsutsui, S. Haraguchi, K. Inoue, H. Miyabara, T. Ubuka, M. Hatori, T. Hirota, Y. Fukada
  • Journal Title: J. Exp. Neurosci. Volume: 7 Pages: 15-29
  • DOI: 10.4137/JEN.S11148
  • Peer Reviewed
• [Journal Article] Review: 10th International Symposium on Avian Endocrinology (2013)
  • Author(s): K. Tsutsui, P. J. Sharp, R. M. Dores
  • Journal Title: Gen. Comp. Endocrinol. Volume: 190 Pages: 1-2
  • DOI: 0.1016/j.ygcen.2013.03.011
  • Peer Reviewed
• [Journal Article] Review: Regulatory mechanisms of gonadotropin-inhibitory hormone (GnIH) synthesis and release in photoperiodic animals (2013)
  • Author(s): K. Tsutsui, T. Ubuka, G. E. Bentley, L. Kriegsfeld
  • Journal Title: Front. Neurosci. Volume: 7 Pages: 1-11
  • DOI: 10.3389/fnins.2013.00060
  • Peer Reviewed
• [Journal Article] Review: Neuroendocrine regulation of gonadotropin secretion in seasonally breeding birds (2013)
  • Author(s): T. Ubuka, G. E. Bentley, K. Tsutsui
  • Journal Title: Front. Neurosci. Volume: 7 Pages: 1-17
  • DOI: 10.3389/fnins.2013.00038
  • Peer Reviewed
• [Journal Article] Review: Brain and pineal 7alpha-hydroxypregnenolone stimulating locomotor activity: identification, mode of action and regulation of biosynthesis (2013)
  • Author(s): K. Tsutsui, S. Haraguchi, Y. Fukada, H. Vaudry
  • Journal Title: Front. Neuroendocrinol. Volume: 34 Pages: 179-189
  • DOI: 10.1016/j.yfrne.2013.05.002
  • Peer Reviewed
• [Journal Article] Review: Identification, localization and function of a novel neuropeptide, 26RFa, and its cognate receptor, GPR103 in the avian hypothalamus (2013)
  • Author(s): K. Ukena, T. Tachibana, Y. Tobari, J. Leprince, H. Vaudry, K. Tsutsui
  • Journal Title: Gen. Comp. Endocrinol. Volume: 190 Pages: 42-46
  • DOI: 10.1016/j.ygcen.2013.03.014
  • Peer Reviewed
• [Journal Article] Review: Gonadotropin-inhibitory hormone (GnIH), GnIH receptor and cell signaling (2013)
  • Author(s): T. Ubuka, Y. L. Son, G. E. Bentley, R. P. Millar, K. Tsutsui
  • Journal Title: Gen. Comp. Endocrinol. Volume: 190 Pages: 10-17
  • DOI: 10.1016/j.ygcen.2013.02.030
  • Peer Reviewed
• [Journal Article] Review: RNA interference of gonadotropin-inhibitory hormone gene induces aggressive and sexual behaviors in birds (2013)
  • Author(s): T. Ubuka, T. Mizuno, Y. Fukuda, G. E. Bentley, J. C. Wingfield, K. Tsutsui
  • Journal Title: Gen. Comp. Endocrinol. Volume: 181 Pages: 179-186
  • DOI: 10.1016/j.ygcen.2012.09.010
  • Peer Reviewed
• [Journal Article] Review: Melatonin stimulates the synthesis and release of gonadotropin-inhibitory hormone in birds (2013)
  • Author(s): V. S. Chowdhury, T. Ubuka, K. Tsutsui
  • Journal Title: Gen. Comp. Endocrinol. Volume: 181 Pages: 175-178
  • DOI: 10.1016/j.ygcen.2012.08.005
  • Peer Reviewed
• [Journal Article] Review: Create new research directions in comparative endocrinology from Asia and Oceania (2013)
  • Author(s): K. Tsutsui
  • Journal Title: Gen. Comp. Endocrinol. Volume: 181 Pages: 192-196
  • DOI: 10.1016/j.ygcen.2012.04.015
  • Peer Reviewed
• [Journal Article] 総説：ハムスターのGnIHの同定及び発現制御と生理機能の解析 (2013)
  • Author(s): 産賀崇由、井上和彦、筒井和義
  • Journal Title: 生殖内分泌学会雑誌 Volume: 18 Pages: 27-33
  • Peer Reviewed
• [Journal Article] 総説：松果体で合成・放出されたアロプレグナノロンは発達期の小脳プルキンエ細胞の生存に不可欠である (2013)
  • Author(s): 原口省吾、原桜子、産賀崇由、三田雅敏、筒井和義
  • Journal Title: 比較内分泌学 Volume: 39 Pages: 44-48
  • Peer Reviewed
• [Journal Article] Backdoor pathway for dihydrotestosterone biosynthesis: implications for normal and abnormal human sex development (2013)
  • Author(s): M. Fukami, K. Homma, T. Hasegawa, T. Ogata
  • Journal Title: Dev. Dyn. Volume: 242 Pages: 320-329
  • DOI: 10.1002/dvdy.23892
  • Peer Reviewed
• [Journal Article] De novo frameshift mutation in fibroblast growth factor 8 in a male patient with gonadotropin deficiency (2013)
  • Author(s): E. Suzuki, S. Yatsuga, M. Igarashi, M. Miyado, K. Nakabayashi, K. Hayashi, K. Hata, A. Umezawa, G. Yamada, T. Ogata, M. Fukami
  • Journal Title: Horm. Res. Paediatr. Volume: 81 Pages: 139-144
  • DOI: 10.1159/000355380
  • Peer Reviewed
• [Journal Article] Genomic basis of aromatase excess syndrome: recombination- and replication-mediated rearrangements leading to CYP19A1 overexpression (2013)
  • Author(s): M. Fukami, T. Tsuchiya, H. Vollbach, K. A. Brown, S. Abe, S. Ohtsu, M. Wabitsch, H. Gurger, E. R. Sompson, A. Emezawa, K. Nakabayashi, S. E. Bulun, M. Shozu, T. Ogata
  • Journal Title: J. Clin. Endocrinol. Metab. Volume: 98 Pages: E2013-E2021
  • DOI: 10.1210/jc.2013-2520
  • Peer Reviewed
• [Journal Article] A novel de novo point mutation of OCT-binding site in the IGF2/H19-imprinting control region in a patient with Beckwith-Wiedemann syndrome (2013)
  • Author(s): K. Higashimoto, K. Jozaki, T. Kosho, K. Matsubara, T. Sato, D. Yamada, H. Yatsuki, T. Maeda, Y. Ohtsuka, K. Nishioka, K. Joh, H. Koseki, T. Ogata, H. Soejima
  • Journal Title: Clin. Genet. Volume: 印刷中 Pages: in press
  • DOI: 10.1111/cge.12318.2013
  • Peer Reviewed
• [Journal Article] Critical role of Yp inversion in PRKX/PRKY-mediated Xp;Yp translocation in a patient with 45, X testicular disorder of sex development (2013)
  • Author(s): S. Nakashima, Y. Watanabe, J. Okada, H. Ono, E. Nagata, M. Fukami, T. Ogata
  • Journal Title: Endocr. J. Volume: 60 Pages: 1329-1334
  • Peer Reviewed
• [Journal Article] Aromatase excess syndrome in a family with upstream deletion of CYP19A1 (2013)
  • Author(s): D. Shihara, M. Miyado, K. Nakabayashi, M. Shozu, K. Nagasaki, T. Ogata, M. Fukami
  • Journal Title: Clin. Endocrinol. Volume: 印刷中 Pages: in press
  • DOI: 10.1111/cen.12329
  • Peer Reviewed
• [Journal Article] Identification of AP2S1 mutation and effects of low calcium formula in an infant with hypercalcemia and hypercalciuria (2013)
  • Author(s): Y. Fujisawa, R. Yamaguchi, E. Satake, K. Ohtaka, T. Nakanishi, K. Ozono, T. Ogata
  • Journal Title: J. Clin. Endocrinol. Metab. Volume: 98 Pages: E2022-E2027
  • DOI: 10.1210/jc.2013-2571
  • Peer Reviewed
• [Journal Article] The lipid fraction of human milk initiates adipocyte differentiation in 3T3-L1 cells (2013)
  • Author(s): Y. Fujisawa, R. Yamaguchi, E. Nagata, E. Satake, S. Sano, R. Matsushita, K. Kitsuta, S. Nakashima, T. Nakanishi, Y. Nakagawa, T. Ogata
  • Journal Title: Early Hum. Dev. Volume: 89 Pages: 713-719
  • DOI: 10.1016/j.earlhumdev.2013.05.002
  • Peer Reviewed
• [Journal Article] A 68-year-old phenotypically male patient with 21-hydroxylase deficiency and concomitant adrenocortical neoplasm producing testosterone and cortisol (2013)
  • Author(s): M. Hayashi, Y. Kataoka, Y. Sugimura, F. Kato, M. Fukami, T. Ogata, K. Homma, T. Hasegawa, Y. Oiso, H. Sasano, H. Tanaka
  • Journal Title: Tohoku J. Exp. Med. Volume: 231 Pages: 75-84
  • Peer Reviewed
• [Journal Article] Cryptic genomic rearrangements in three patients with 46,XY disorders of sex development (2013)
  • Author(s): M. Igarashi, V. C. Dung, E. Suzuki, S. Ida, M. Nakacho, K. Nakabayashi, K. Mizuno, Y. Hayashi, K. Kohri, Y. Kojima, T. Ogata, M. Fukami
  • Journal Title: PLoS. One Volume: 8 Pages: e68194
  • DOI: 10.1371/journal.pone.0068194
  • Peer Reviewed
• [Journal Article] Gain-of-function mutations in RIT1 cause Noonan syndrome, a RAS/MAPK pathway syndrome (2013)
  • Author(s): Y. Aoki, T. Niihori, T. Banjo, N. Okamoto, S. Mizuno, K. Kurosawa, T. Ogata, F. Takada , M. Yano, T. Ando, T. Hoshika, C. Barnett, H. Ohashi, H. Kawame, T. Hasegawa, T. Okutani, T. Nagashima, S. Hasegawa, R. Funayama, T. Nagashima, K. Nakayama, S. Inoue, Y. Watanabe, T. Ogura, Y. Matsubara
  • Journal Title: Am. J. Hum. Genet. Volume: 93 Pages: 173-180
  • DOI: 10.1016/j.ajhg.2013.05.021
  • Peer Reviewed
• [Journal Article] Glucose-6-phosphate dehydrogenase deficiency and adrenal hemorrhage in a Filipino neonate with hyperbilirubinemia (2013)
  • Author(s): A. Ohishi, D. Ueno, T. Ogata
  • Journal Title: AJP. Rep. Volume: 3 Pages: 5-8
  • DOI: 10.1055/s-0032-1329125
  • Peer Reviewed
• [Journal Article] MLL2 and KDM6A mutations in patients with Kabuki syndrome (2013)
  • Author(s): N. Miyake, E. Koshimizu, N. Okamoto, S. Mizuno, T. Ogata, T. Nagai, T. Kosho, H. Ohashi, M. Kato, G. Sasaki, H. Mabe, Y. Watanabe, M. Yoshino, T. Matsuishi, J. Takanashi, V. Shotelersuk, M. Tekin, N. Ochi, M. Kubota, N. Ito, K. Ihara, T. Hara, H. Tonoki, T. Ohta, K. Saito, M. Matsuo, M. Urano, et al
  • Journal Title: Am. J. Med. Genet. A Volume: 161 Pages: 2234-2243
  • DOI: 10.1002/ajmg.a.36072
  • Peer Reviewed
• [Journal Article] Human glutathione S-transferase A (GSTA) family genes are regulated by steroidogenic factor 1 (SF-1) and are involved in steroidogenesis (2013)
  • Author(s): T. Matsumura, Y. Imamichi, T. Mizutani, Y. Ju, T. Yazawa, S. Kawabe, M. Kanno, T. Ayabe, N. Katsumata, M. Fukami, M. Inatani, Y. Akagi, A. Umezawa, T. Ogata, K. Miyamoto
  • Journal Title: FASEB. J. Volume: 27 Pages: 3198-3208
  • DOI: 10.1096/fj.12-222745
  • Peer Reviewed
• [Journal Article] Submicroscopic deletion involving the fibroblast growth factor receptor 1 gene in a patient with combined pituitary hormone deficiency (2013)
  • Author(s): M. Fukami, M. Iso, N. Sato, M. Igarashi, M. Seo, I. Kazukawa, E. Kinoshita, S. Dateki, T. Ogata
  • Journal Title: Endocr. J. Volume: 60 Pages: 1013-1020
  • Peer Reviewed
• [Journal Article] A novel homozygous mutation of the nicotinamide nucleotide transhydrogenase gene in a Japanese patient with familial glucocorticoid deficiency (2013)
  • Author(s): R. Yamaguchi, F. Kato, T. Hasegawa, N. Katsumata, M. Fukami, T. Matsui, K. Nagasaki, T. Ogata
  • Journal Title: Endocr. J. Volume: 60 Pages: 855-859
  • Peer Reviewed
• [Journal Article] Birth seasonality in Prader-Willi syndrome resulting from chromosome 15 microdeletion (2013)
  • Author(s): T. Ayabe, K Matsubara, T. Ogata, A. Ayabe, N. Murakami, T. Nagai, M. Fukami
  • Journal Title: Am. J. Med. Genet. A Volume: 161A Pages: 1495-1497
  • DOI: 10.1002/ajmg.a.35893
  • Peer Reviewed
• [Journal Article] Molecular and clinical studies in 138 Japanese patients with Silver-Russell syndrome (2013)
  • Author(s): T. Fuke, S. Mizuno, T. Nagai, T. Hasegawa, R. Horikawa, Y. Miyoshi, K. Muroya, T. Kondoh, C. Numakura, S. Sato, K. Nakabayashi, C. Tayama, K. Hata, S. Sano, K. Matsubara, M. Kagami, K. Yamazawa, T. Ogata
  • Journal Title: PLoS. One Volume: 8 Pages: e60405
  • DOI: 10.1371/journal.pone.0060105
  • Peer Reviewed
• [Journal Article] Neuromuscular symptoms in a patient with familial pseudohypoparathyroidism type Ib diagnosed by methylation-specific multiplex ligation-dependent probe amplification (2013)
  • Author(s): K. Nagasaki, S. Tsuchuya, A. Saitoh, T. Ogata, M. Fukami
  • Journal Title: Endocr. J. Volume: 60 Pages: 231-236
  • Peer Reviewed
• [Journal Article] Possible contribution of fetal size and gestational age to myocardial tissue Doppler velocities in preterm fetuses (2013)
  • Author(s): K. Sekii, H. Itoh, T. Ogata, S. Iwashima
  • Journal Title: Eur. J. Obstet. Gynecol. Reprod. Biol. Volume: 167 Pages: 121
  • DOI: 10.1016/j.ejogrb.2012.09.027
  • Peer Reviewed
• [Journal Article] A report of two novel NR5A1 mutation families: possible clinical phenotype of psychiatric symptoms of anxiety and/or depression (2013)
  • Author(s): A. S. Suwanai, T. Ishii, H. Haruna, A. Yamataka, S. Narumi, R. Fukuzawa, T. Ogata, T. Hasegawa
  • Journal Title: Clin. Endocrinol. Volume: 78 Pages: 957-965
  • DOI: 10.1111/cen.12054
  • Peer Reviewed
• [Journal Article] Review: Advanced maternal age at childbirth and the development of uniparental disomy. A commentary on the proportion of uniparental disomy is increased in Prader-Willi syndrome due to an advanced maternal childbearing age in Korea (2013)
  • Author(s): K. Matsubara, T. Ogata
  • Journal Title: J. Hum. Genet. Volume: 58 Pages: 118-119
  • DOI: 10.1038/jhg.2013.4
  • Peer Reviewed
• [Presentation] Progress in comparative endocrinology by discovering novel neuropeptides and neurosteroids (特別講演) (2014)
  • Author(s): K. Tsutsui
  • Organizer: The 7th Intercongress symposium of the Asia and Oceania Society for the Comparative Endocrinology (AOSCE)
  • Place of Presentation: National Taiwan Ocean University, Keelung, Taiwan
  • Year and Date: 20140318-20140324
  • Invited
• [Presentation] Pineal allopregnanolone saves purkinje cells from apoptosis in the cerebellum (2014)
  • Author(s): S. Haraguchi, S. Hara, T. Ubuka, K. Tsutsui
  • Organizer: The 7th Intercongress symposium of the AOSCE
  • Place of Presentation: National Taiwan Ocean University, Keelung, Taiwan
  • Year and Date: 20140318-20140324
• [Presentation] Transcriptional activation of gonadotropin-inhibitory hormone by corticosterone (2014)
  • Author(s): Y. L. Son, T. Ubuka, M. Narihiro, Y. Fukuda, I. Hasunuma, K. Yamamoto, D. D. Belsham, K. Tsutsui
  • Organizer: The 7th Intercongress symposium of the AOSCE
  • Place of Presentation: National Taiwan Ocean University, Keelung, Taiwan
  • Year and Date: 20140318-20140324
• [Presentation] 生殖を抑制する新規脳ホルモンの発見と研究進展：鳥類から哺乳類への展開 （招待講演） (2013)
  • Author(s): 筒井和義
  • Organizer: 第2回実験動物科学シンポジウム－新たなライフサイエンス研究の展開－鳥類リソースの整備と活用に向けて－
  • Place of Presentation: 名古屋大学野依記念学術交流館（名古屋市千種区）
  • Year and Date: 20131209-20131209
  • Invited
• [Presentation] The signaling pathway mediating the inhibitory effect of gonadotropin-inhibitory hormone (GnIH) in gonadotropes and GnRH neurons (2013)
  • Author(s): Y. L. Son, T. Ubuka, K. Tsutsui
  • Organizer: 第18回日本生殖内分泌学会学術集会
  • Place of Presentation: シェーンバッハ・サボー（東京都千代田区）
  • Year and Date: 20131207-20131207
• [Presentation] Biosynthesis and biological action of pineal neurosteroids in birds (2013)
  • Author(s): K. Tsutsui, S. Haraguchi
  • Organizer: 第37回鳥類内分泌研究会
  • Place of Presentation: アソシエート（熊本県阿蘇郡）
  • Year and Date: 20131121-20131122
• [Presentation] Neuroendocrine mechanisms translating social stimuli into reproductive physiology and behavior (2013)
  • Author(s): Y. Tobari, Y. L. Son, T. Ubuka, Y. Hasegawa, K. Tsutsui
  • Organizer: 第37回鳥類内分泌研究会
  • Place of Presentation: アソシエート（熊本県阿蘇郡）
  • Year and Date: 20131121-20131122
• [Presentation] 視床下部ホルモンの比較内分泌学（招待講演） (2013)
  • Author(s): 筒井和義
  • Organizer: 第38回日本比較内分泌学会大会・小林英司先生記念シンポジウム
  • Place of Presentation: 宮崎市民プラザ（宮崎県宮崎市）
  • Year and Date: 20131024-20131026
  • Invited
• [Presentation] 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 (2013)
  • Author(s): 鈴木悠子、原口省吾、山本雄三、張雋螢、小山鉄平、三田雅敏、上田宏、筒井和義
  • Organizer: 第38回日本比較内分泌学会大会・小林英司先生記念シンポジウム
  • Place of Presentation: 宮崎市民プラザ（宮崎県宮崎市）
  • Year and Date: 20131024-20131026
• [Presentation] 精巣由来アンドロゲンによる脳内7alpha-ヒドロキシプレグネノロン合成制御 (2013)
  • Author(s): 原口省吾、鈴木悠子、田代渓一郎、三田雅敏、筒井和義
  • Organizer: 第38回日本比較内分泌学会大会・小林英司先生記念シンポジウム
  • Place of Presentation: 宮崎市民プラザ（宮崎県宮崎市）
  • Year and Date: 20131024-20131026
• [Presentation] Gonadotropin-inhibitory hormone (GnIH), a new key neurohormone regulating reproduction: Discovery, progress and perspective（特別講演） (2013)
  • Author(s): K. Tsutsui
  • Organizer: The International Conference on Comparative Endocrinology and Physiology (ICCEP-2013)
  • Place of Presentation: RTM Nagpur University, Nagpur, India
  • Year and Date: 20131021-20131023
  • Invited
• [Presentation] 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 (2013)
  • Author(s): 鈴木悠子、原口省吾、山本雄三、張雋螢、小山鉄平、三田雅敏、上田宏、筒井和義
  • Organizer: 第84回日本動物学会大会
  • Place of Presentation: 岡山大学津島キャンパス（岡山県岡山市）
  • Year and Date: 20130926-20130928
• [Presentation] 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 (2013)
  • Author(s): 原口省吾、原桜子、産賀崇由、三田雅敏、筒井和義
  • Organizer: 第84回日本動物学会大会
  • Place of Presentation: 岡山大学津島キャンパス（岡山県岡山市）
  • Year and Date: 20130926-20130928
• [Presentation] GnIHによるGnRHニューロン内シグナリング抑制機構 (2013)
  • Author(s): 孫ユリ、産賀崇由、筒井和義
  • Organizer: 第84回日本動物学会大会
  • Place of Presentation: 岡山大学津島キャンパス（岡山県岡山市）
  • Year and Date: 20130926-20130928
• [Presentation] 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 (2013)
  • Author(s): 産賀崇由、原口省吾、原田信弘、筒井和義
  • Organizer: 第84回日本動物学会大会
  • Place of Presentation: 岡山大学津島キャンパス（岡山県岡山市）
  • Year and Date: 20130926-20130928
• [Presentation] 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 (2013)
  • Author(s): 戸張靖子、孫ユリ、産賀崇由、長谷川喜久、筒井和義
  • Organizer: 第84回日本動物学会大会
  • Place of Presentation: 岡山大学津島キャンパス（岡山県岡山市）
  • Year and Date: 20130926-20130928
• [Presentation] Kiss2の分子進化に関する研究 (2013)
  • Author(s): 大杉知裕、大滝直仁、砂川裕哉、孫ユリ、大久保誠、飯郷雅之、天野勝文、筒井和義
  • Organizer: 第84回日本動物学会大会
  • Place of Presentation: 岡山大学津島キャンパス（岡山県岡山市）
  • Year and Date: 20130926-20130928
• [Presentation] Genetic advances in DSD (招待講演) (2013)
  • Author(s): T. Ogata
  • Organizer: The Joint Summer School for Pediatric Endocrinology
  • Place of Presentation: Castello Dal Pozzo, Lake Maggiore, Italy.
  • Year and Date: 20130922-20130925
  • Invited
• [Presentation] GnIHによる視床下部P450arom活性の制御と性差 (2013)
  • Author(s): 産賀崇由、筒井和義
  • Organizer: 新学術領域研究「性差構築の分子基盤」第5回領域会議
  • Place of Presentation: 国民宿舎虹の松原ホテル（佐賀県唐津市）
  • Year and Date: 20130905-20130907
• [Presentation] Breakthrough in neuroendocrinology by discovering novel neuropeptides and neurosteroids (特別講演: Bargmann-Scharrer Lecture) (2013)
  • Author(s): K. Tsutsui
  • Organizer: The 17th International Congress of Comparative Endocrinology (ICCE)
  • Place of Presentation: University of Barcelona, Barcelona, Spain
  • Year and Date: 20130715-20130719
  • Invited
• [Presentation] Pineal allopregnanolone saves cerebellar Purkinje cells from apoptosis （招待講演） (2013)
  • Author(s): S. Haraguchi, S. Hara, T. Ubuka, M. Mita, K. Tsutsui
  • Organizer: The 17th International Congress of Comparative Endocrinology (ICCE)
  • Place of Presentation: University of Barcelona, Barcelona, Spain
  • Year and Date: 20130715-20130719
  • Invited
• [Presentation] Female presence increases gonadotropin-inhibitory hormone gene expression by decreasing norepinephrine in the male quail brain （招待講演） (2013)
  • Author(s): Y. Tobari, Y. L. Son, Y. Hasegawa, K. Tsutsui
  • Organizer: The 17th International Congress of Comparative Endocrinology (ICCE)
  • Place of Presentation: University of Barcelona, Barcelona, Spain
  • Year and Date: 20130715-20130719
  • Invited
• [Presentation] Gonadotropin-inhibitory hormone inhibits AC/cAMP/PKA-mediated signaling pathway in gonadotropes and GnRH neurons (2013)
  • Author(s): Y. L. Son, T. Ubuka, R. P. Millar, K. Tsutsui
  • Organizer: The 17th International Congress of Comparative Endocrinology (ICCE)
  • Place of Presentation: University of Barcelona, Barcelona, Spain
  • Year and Date: 20130715-20130719
• [Presentation] Gonadotropin-inhibitory hormone inhibits aggressive behavior by increasing estrogen synthesis in the brain beyond its optimum concentration (2013)
  • Author(s): T. Ubuka, S. Haraguchi, N. Harada, K. Tsutsui
  • Organizer: The 17th International Congress of Comparative Endocrinology (ICCE)
  • Place of Presentation: University of Barcelona, Barcelona, Spain
  • Year and Date: 20130715-20130719
• [Presentation] 視床下部ホルモンの発見と比較内分泌学の進展（招待講演） (2013)
  • Author(s): 筒井和義
  • Organizer: 東京大学大気海洋研究所共同利用研究集会－海洋生物のさまざまな適応戦略
  • Place of Presentation: 東京大学大気海洋研究所（千葉県柏市）
  • Year and Date: 20130622-20130622
  • Invited
• [Presentation] 脳におけるprogesteroneとallopregnanoloneの生合成と生理作用（招待講演） (2013)
  • Author(s): 筒井和義
  • Organizer: 第2回プロゲストーゲン研究会
  • Place of Presentation: 第一ホテル東京（東京都港区）
  • Year and Date: 20130518-20130518
  • Invited
• [Presentation] Genetics of Combined Pituitary Hormone Deficiency. In: Symposium, Neuroendocrinology, Novel Players in Pituitary Disorders (招待講演) (2013)
  • Author(s): T. Ogata
  • Organizer: 2013 Seoul International Congress of Endocrinology and Metabolism (SICEM) in conjunction with the 32nd Annual Meeting of the Korean Endocrine Society
  • Place of Presentation: Grand Hilton Seoul Hotel, Seoul, South Korea.
  • Year and Date: 20130502-20130505
  • Invited
• [Presentation] 生殖補助医療と小児医療の接点：オーバービュー（招待講演） (2013)
  • Author(s): 緒方勤
  • Organizer: 第116回日本小児科学会学術集会
  • Place of Presentation: 広島市文化交流会館（広島市中区）
  • Year and Date: 20130419-20130421
  • Invited
• [Book] スクエア 最新図説生物（二訂版）高等学校 (2014)
  • Author(s): 筒井和義
  • Total Pages: 344
  • Publisher: 第一学習社
• [Book] Special Issue of the 10th International Symposium on Avian Endocrinology (2013)
  • Author(s): K. Tsutsui, P. J. Sharp, R. M. Dores
  • Total Pages: 235
  • Publisher: Gen. Comp. Endocrinol.
• [Book] The E-Book of Neurosteroids: Frontiers Research Topic (2013)
  • Author(s): H. Vaudry, K. Tsutsui
  • Total Pages: 476
  • Publisher: Frontiers in Endocrinology (http://flashbook.frontiersin.org//clients/Frontiers/Neurosteroids/EBook.html)
• [Book] Neurosteroids and synaptic formation in the cerebellum. In: Handbook of Cerebellum and Cerebellar Disorders (2013)
  • Author(s): K. Tsutsui
  • Total Pages: 2397 (993-1012)
  • Publisher: Springer
• [Book] Gonadotropin-inhibitory hormone (GnIH). In: The Handbook of Biologically Active Peptides (2nd edition) (2013)
  • Author(s): K. Tsutsui, T. Ubuka
  • Total Pages: 1943 (802-811)
  • Publisher: Elsevier publisher
• [Book] 26RFa. In: The Handbook of Biologically Active Peptides (2nd edition) (2013)
  • Author(s): J. Leprince, C. Neveu, B. Lefrance, L. Guilhaudis, I. Segalas-Milazzo, J.-C. Do Rego, M. Tena-Sempere, K. Tsutsui, H. Vaudry
  • Total Pages: 1943 (917-923)
  • Publisher: Elsevier publisher
• [Book] 産婦人科疾患最新の治療2013-2015 (2013)
  • Author(s): 緒方勤
  • Total Pages: 308（297-298）
  • Publisher: 南江堂