Molecular Mechanisms of Neuronal Diseases Caused by Sex Hormones

• Project/Area Number: 19790225
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Single-year Grants
• Research Field: Pathological medical chemistry
• Research Institution: The University of Tokyo
• Principal Investigator: MATSUMOTO Takahiro The University of Tokyo, 分子細胞生物学研究所, 協力研究員 (70447374)
• Project Period (FY): 2007 – 2008
• Project Status: Completed (Fiscal Year 2008)
• Budget Amount: ¥3,780,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥480,000); Fiscal Year 2008: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000); Fiscal Year 2007: ¥1,700,000 (Direct Cost: ¥1,700,000)
• Keywords: 分子病態学 / 転写 / 性ステロイドホルモン / 精神神経疾患 / 性染色体

Research Abstract

本研究では性ステロイドホルモン作用と性染色体による性特異性の観点より、クロマチン修飾を介した転写とエピジェネティックスに着目した精神神経疾患の分子メカニズムの解明を試みた。そのアプローチとして脳神経特異的なconditional knockout法による精神神経疾患モデルマウスの確立とタンパク精製による精神神経疾患関連タンパク複合体の同定を試みた。その結果、性ステロイドホルモン受容体の精神機能における重要性及びその標的遺伝子の遺伝子発現制御を介した精神神経疾患発症への寄与を個体レベルで明確にした。また、性特異的染色体より発現する性特異的因子のクロマチン修飾を介した転写制御とエピジェネティックスの分子機構をin vitro系解析により解明しつつある。

Research Products

• [Journal Article] Molecular mechanisms underlying the effects of sex steroids on bone and mineral metabolism. (2009)
  • Author(s): Imai, Y., Nakamura, T., Matsumoto, T., Takaoka, K., Kato, S.
  • Journal Title: J. Bone. Miner. Metab. in press
  • NAID: 10025336521
  • Peer Reviewed
• [Journal Article] Coactivation of estrogen receptor b by a gonadotropin-induced cofactor GIOT. (2009)
  • Author(s): Kouzu-Fujita, M., Mezaki, Y., Mtsumoto, T., Yamaoka, I., Sawatsubashi, S., Yano, T., Taketani, Y., Kitagawa, H., Kato, S.
  • Journal Title: Mol. Cell. Biol. 29 Pages: 83-92
  • Peer Reviewed
• [Journal Article] Spermatogenesis-specific association of SMCY and MSH5. (2008)
  • Author(s): Akimoto, C., Kitagawa, H., Matsumoto, T., Kato, S.
  • Journal Title: Genes to Cells 13 Pages: 623-633
  • Peer Reviewed
• [Journal Article] Androgen receptor functions in male and female physiology. (2008)
  • Author(s): Matsumoto, T., Shiina, H., Kawano, H., Sato, T., Kato, S.
  • Journal Title: J. Steroid Biochem. Mol. Biol. 109 Pages: 236-241
• [Journal Article] Dihydrotestosterone inhibits murine hair growth via the androgen receptor (2008)
  • Author(s): Naito, A.
  • Journal Title: British Journal of Dermatology 159 Pages: 300-305
  • Peer Reviewed
• [Journal Article] Spermatogenesis-specific association of SMCY and MSH5 (2008)
  • Author(s): Akimoto, C.
  • Journal Title: Genes to Cells 13 Pages: 623-633
  • Peer Reviewed
• [Journal Article] Androgen receptor functions in male and female physiology (2008)
  • Author(s): Matsumoto, T.
  • Journal Title: Journal of Steroid Biochemistry and Molecular Biology 109 Pages: 236-241
• [Journal Article] Estrogen prevents bone loss via estrogen receptor a and induction of Fas ligand in osteoclasts. (2007)
  • Author(s): Nakamura, T., Imai, Y., Matsumoto, T., Sato, S., Takeuchi, K., Igarash, K., Harada, Y., Azuma, Y., Krust, A., Yamamoto, Y., Nishina, H., Takeda, S., Takayanagi, H., Metzger, D., Kanno, J., Takaoka, K., Martin, T. J., Chambon, P., Kato, S.
  • Journal Title: Cell 130 Pages: 811-823
  • Peer Reviewed
• [Journal Article] Pituitary function of androgen receptor constitutes a glucocorticoid production circuit. (2007)
  • Author(s): Miyamoto, J., Matsumoto, T., Shiina, H., Inoue, K., Takada, I., Ito, S., Itoh, J., Minematsu, T., Sato, T., Yanase, T., Nawata, H., Osamura, R. Y., Kato, S.
  • Journal Title: Mol. Cell. Biol. 27 Pages: 4807-4814
  • Peer Reviewed
• [Journal Article] Androgen receptor functions in male and female reproduction. (2007)
  • Author(s): Matsumoto, T., Kawano, H., Shiina, H., Sato,T., Kato, S.
  • Journal Title: Reproductive Med. Biol. 6 Pages: 11-17
  • NAID: 10018849528
• [Journal Article] Strain-dependent embryonic lethality and exaggerated vascular remodeling in heparin cofactor II-deficient mice. (2007)
  • Author(s): Aihara, K., Azuma, H., Akaike, M., Ikeda, Y., Sata, M., Takamori, N., Yagi, S., Iwase,T., Sumitomo, Y., Kawano, H., Yamada, T., Fukuda, T., Matsumoto, T., Sekine, K., Sato,T., Nakamichi, Y., Yamamoto, Y., Yoshimura, K., Watanabe, T., Nakamura, T., Oomizu, A., Tsukada, M., Hayashi, H., Sudo,T., Kato, S., Matsumoto, T.
  • Journal Title: J. Clin. Invest. 117 Pages: 1514-1526
  • Peer Reviewed
• [Journal Article] Androgen receptor functions in male and female reproduction (2007)
  • Author(s): Matsumoto. T., et. al.(他4名)
  • Journal Title: Reproductive Medicine and Biology 6 Pages: 11-17
  • NAID: 10018849528
• [Journal Article] Estrogen prevents bone loss via estrogen receptor α and induction of Fas ligand in osteoclast (2007)
  • Author(s): Nakanura T., Imai Y., Matsumoto T., et. al.(他15名)
  • Journal Title: Cell 130 Pages: 811-823
  • Peer Reviewed
• [Journal Article] Pituitary function of androgen receptor constitutes a glucocorticoid production circuit (2007)
  • Author(s): Miyamoto J., Matsumoto T., (他11名)
  • Journal Title: Molecular and Cellular Biology 27 Pages: 4807-4814
  • Peer Reviewed
• [Presentation] Androgen receptor functions in brain sexual differentiation and behaviors (2008)
  • Author(s): Matsumoto, T.
  • Organizer: International symposium for gonad and brain sex differentiation
  • Place of Presentation: 福岡
  • Year and Date: 2008-10-16
• [Presentation] 骨芽細胞におけるエストロゲンの作用の解明-骨芽細胞特異的エストロゲン受容体欠損マウスを用いて (2008)
  • Author(s): 金藤紫乃, 今井祐記, 高田伊知郎, 中村貴, 松本高広, 加藤茂明
  • Organizer: 第31回日本分子生物学会, 第81回日本生化学会合同大会
  • Place of Presentation: 神戸
• [Presentation] DEAD-box RNA helicase is required for Drosha-madiating processing of a subset of microRNAs. (2008)
  • Author(s): Inoue, K., T. Matsumoto, T., Yamagata, K., Akimoto, C., Yonezawa, M., Kato, S.
  • Organizer: 2008 Keystone Symposia Conference (RNAi, MicroRNA, and Non-Codin RNA).
  • Place of Presentation: Whistler, Canada
• [Presentation] Y染色体遺伝子TSPYと男性ホルモン受容体の機能的相互作用の解析 (2007)
  • Author(s): 秋本千央, 上田崇, 山岡育子, 井上和樹, 松本高広, 盛真友, 北川浩史, 加藤茂明
  • Organizer: 第30回日本分子生物学会, 第80回日本生化学会合同大会
  • Place of Presentation: 横浜
• [Presentation] エストロゲンの骨量維持機構はFas Lignd シグナルを介した破骨細胞寿命の調節である (2007)
  • Author(s): 今井祐記, 中村貴, 竹田秀, 福田亨, 山本陽子, 高岡邦夫, 松本高広, 加藤茂明
  • Organizer: 第25回日本骨代謝学会
  • Place of Presentation: 大阪