Dysregulation of intra-ovarian theca cell-androgen axis in women with gonadotropin-poor responsiveness and polycystic ovary syndrome

• Project/Area Number: 24592464
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Obstetrics and gynecology
• Research Institution: University of Fukui
• Principal Investigator: ORISAKA Makoto 福井大学, 医学部附属病院, 講師 (80324143)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000); Fiscal Year 2014: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2013: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2012: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
• Keywords: 莢膜細胞 / アンドロゲン / 卵胞発育 / ゴナドトロピン不応症 / PCOS / 排卵誘発 / 細胞間クロストーク / 黄体化ホルモン / 多嚢胞性卵巣症候群 / poor responder / ovary / follicle / androgen

Outline of Final Research Achievements

Ovarian androgens produced by theca cells induce granulosa cell proliferation and early follicle growth. Dysregulation of theca cell-androgen axis leads to ovarian pathology such as gonadotropin poor-responsiveness (poor responder) and polycystic ovary syndrome (PCOS). Inactivation of theca cell-androgen axis in poor responder and hyperactivation of theca cell-androgen axis in PCOS can cause downregulation of FSH receptor expression in granulosa cells, resulting in poor response to gonadotropin stimulation. Normalization of androgen levels in ovaries of poor responder and PCOS would contribute the expression of FSH receptor in granulosa cells and the acquisition of gonadotropin responsiveness in growing follicles.

Research Products

• [Journal Article] Protective effect of dienogest on chemotherapy-induced reduced fertility in female rats (2015)
  • Author(s): H.Tsuyoshi, M.Orisaka, S.Fukuda, K.Hattori, BK.Tsang, Y.Yoshida
  • Journal Title: Steroids Volume: 93 Pages: 1-7
  • DOI: 10.1016/j.steroids.2014.10.010
  • Peer Reviewed
• [Journal Article] Dysregulation of ovarian follicular development in female rat: LH decreases FSH sensitivity during preantral-early antral transition. (2013)
  • Author(s): Orisaka M, Hattori K, Fukuda S, Mizutani T, Miyamoto K, Sato T, Tsang BK, Kotsuji F, Yoshida Y.
  • Journal Title: Endocrinology Volume: 154 Issue: 8 Pages: 2870-2880
  • DOI: 10.1210/en.2012-2173
  • Peer Reviewed
• [Journal Article] A novel isoform of liver receptor homolog-1 is regulated by steroidogenic factor-1 and the specificity protein family in ovarian granulosa cells. (2013)
  • Author(s): Kawabe, S.
  • Journal Title: Endocrinology Volume: 154(4） Issue: 4 Pages: 1648-1660
  • DOI: 10.1210/en.2012-2008
  • Peer Reviewed
• [Presentation] Protective effect of dienogest on chemotherapy-induced reduced fertility female rats (2015)
  • Author(s): M.Orisaka, H.Tsuyoshi, Y.Yoshida
  • Organizer: IFFS/JSRM International Meeting 2015
  • Place of Presentation: 横浜市、パシフィコ横浜
  • Year and Date: 2015-04-26 – 2015-04-29
• [Presentation] 卵胞発育における卵子～顆粒膜細胞～莢膜細胞間のクロストーク (2015)
  • Author(s): 折坂 誠
  • Organizer: 第67回日本産科婦人科学会学術講演会（シンポジウム発表）
  • Place of Presentation: 横浜市、パシフィコ横浜
  • Year and Date: 2015-04-09 – 2015-04-12
• [Presentation] 11-ケトテストステロンはエストロゲン変換を受けないアンドロゲンとして機能する (2015)
  • Author(s): 今道 力敬, 矢澤 隆志, 河邉 真也, 石兼 真, 向井 邦晃, 折坂 誠, 水谷 哲也, 宮本 薫
  • Organizer: 第19回日本生殖内分泌学会学術集会
  • Place of Presentation: 大阪府豊中市、千里ライフサイエンスセンター
  • Year and Date: 2015-01-10
• [Presentation] 不妊治療後の妊娠・分娩はハイリスク！ (2014)
  • Author(s): 折坂 誠
  • Organizer: 第7回福井生殖生物学・医学研究会
  • Place of Presentation: 福井市、ユアーズホテルフクイ
  • Year and Date: 2014-11-06
• [Presentation] 不妊治療後の妊娠・分娩はハイリスク！ (2014)
  • Author(s): 折坂 誠
  • Organizer: 第3回福井県総合周産期勉強会
  • Place of Presentation: 永平寺町、福井大学医学部講義棟
  • Year and Date: 2014-06-22
• [Presentation] ヒト生殖腺におけるHSD11B2の役割 (2014)
  • Author(s): 今道 力敬, 矢澤 隆志, 河邉 真也, 向井邦晃, 折坂 誠, 水谷 哲也, 宮本 薫
  • Organizer: 第87回日本内分泌学会学術集会
  • Place of Presentation: 福岡市、福岡国際会議場・福岡サンパレス
  • Year and Date: 2014-04-24 – 2014-04-26
• [Presentation] 多嚢胞性卵巣症候群における卵胞発育停止メカニズム (2013)
  • Author(s): 折坂 誠
  • Organizer: 第31回 日本受精着床学会 総会・学術講演会
  • Place of Presentation: 大分県別府市・別府国際コンベンションセンター
  • Invited
• [Presentation] Dysregulation of ovarian follicular development in female rat: LH decreases FSH sensitivity during preantral-early antral transition. (2013)
  • Author(s): Orisaka M, Hattori K, Fukuda S, Tsang BK, Yoshida Y.
  • Organizer: 46th Annual Meeting of the Society for the Study of Reproduction
  • Place of Presentation: カナダ・モントリオール
• [Presentation] PCOSの病態解明を目指して (2012)
  • Author(s): 折坂 誠
  • Organizer: 日本内分泌学会 第30回内分泌代謝学サマーセミナー シンポジウム
  • Place of Presentation: 渋川市
  • Invited
• [Presentation] 卵胞発育の基礎知識アップデート (2012)
  • Author(s): 折坂 誠
  • Organizer: 第57回日本生殖医学会学術講演会・総会 シンポジウム
  • Place of Presentation: 長崎市
  • Invited