1999 Fiscal Year Annual Research Report

インヒビン/アクチビンファミリーの作用解析による単一排卵機序の探索

Research Project

Project/Area Number	10470342
Research Institution	Gunma University
Principal Investigator	伊吹令人群馬大学, 医学部, 教授 (40008256)
Co-Investigator(Kenkyū-buntansha)	安部由美子群馬大学, 医学部, 助手 (70261857) 峯岸敬群馬大学, 医学部, 講師 (00209842)
Keywords	インヒビン / アクチビン / フォリスタチン / 卵胞発育
Research Abstract	卵胞発育においてはゴナドトロピンが主要な調節因子であることは周知であるが、局所の成長因子による調節の重要性も近年確認されている。この観点より、activin, follistatin, IGF-I, PRL, adrenomedullin等の種々の成長因子の作用について検討した。DES投与幼弱ラットよりの培養顆粒膜細胞では培養時間の増加に伴い培養液中へのactivin-Aの分泌は増加したが、FSHはこのactivin-Aの増加を抑制した。8-Br-cAMPも同様に抑制したことより、cAMP合成を介した経路によりactivin-A合成が抑制されることが推測された。IGF-Iは単独ではゴナドトロピンレセプターの誘導に作用しないのに対して、FSHによるFSH recepotor,とLH receptorの誘導に対しては促進的に作用すること、このIGF-Iの作用はFSH receptor mRNAとLH receptor mRNAの半減期を延長することによるものであることを明らかとした。PRLは培養5日目以降にFSHによるLH-receptor誘導作用に対し抑制的に作用したが、LH receptor遺伝子の転写の階段には影響せず、LH receptor mRNAの安定性に影響していることが推測された。この顆粒膜細胞にadrenomedullin mRNAを検出し、adrenomedullinの発現はFSHにより抑制されること、hCGはFSHの抑制作用を増強することを発見した。8-Br-cAMPがadrenomedullinの発現を抑制した一方、PMAは影響しなかったことより、FSHの抑制作用はcAMPを介した経路によるものと考えられた。また、adrenomedullinは細胞内cAMPを増加し、FSHのcAMPの増加作用を促進した。これらの結果より、adrenomedullinがautocrine/paracrine作用により、顆粒膜細胞の分化に関与している可能性が考えられた。また、幼弱マウスより得たoocyte-granulosa-theca cell complexではhCG添加によるandrostendion産生とactivin添加によるIR-inhibin産生の促進とestradiol産生がみられたのに対して、酵素処理により得たoocyte-granulosa cell complexではhCG添加によるandrostendion産生もactivin添加によるestradiol産生も共に検出感度以下であった。これらの結果より、activin, follistatinを含む種種の成長因子が卵胞発育に関与しているものと考えられた。

Research Products

(36 results)

All Other

All Publications (36 results)

[Publications] Hirakawa-T: "Effect of prolactin on the expression of luteinizing hormone receptors during cell differentiation in cultured rat granulosa cells"Endocrinology. 140(8). 3444-3451 (1999)
[Publications] Tsuchiya-M: "Control of expression of luteinizing hormone receptor by local factors in rat granulosa calls"Arch-Biochem-Biophys. 367(2). 185-192 (1999)
[Publications] Liu-X: "A comparative study on transforming growth factor-beta and activin A for immature mice. Preantral follicles from adult, immature, and diethylstilbestrol-primed immature mice"Endocrinology. 140(6). 2480-2485 (1999)
[Publications] Kameda-T: "Regulation of cAMP responsive element binding modulator isoforms in cultured rat ovarian granulosa cells"Biochim-Biophys-Acta. 1445(1). 31-38 (1999)
[Publications] Michishita-M: "Expression of adrenomedullin in the endometrium of the human uterus"Obstet-Gynecol. 93(1). 66-70 (1999)
[Publications] Mizunuma-H: "Activin from secondary follicles causes small preantral follicles to remain dormant at the resting stage"Ecdocrinology. 140(1). 37-42 (1999)
[Publications] Kamijo-T: "Biochemical evidence for autocrine/paracrine regulation of apoptosis in cultured uterine epithelial cells during mouse embryo implantation in vitro"Mol-Hum-Reprod. 4(10). 990-998 (1998)
[Publications] Abe-K: "Expression and effect of adrenomedullin on rat granulosa cell"Endocrinology. 139(12). 5263-5266 (1998)
[Publications] Liu-X: "Effects of growth hormone, activin, and follistatin on the development of preantral follicle from immature female mice"Endocrinology. 139(5). 2342-2347 (1998)
[Publications] Kishi-H: "The effect of activin and FSH on the differentiation of rat granulosa cells"FEBS-Lett. 422(2). 274-278 (1998)
[Publications] Minegishi-T: "Control of FSH receptor mRNA expression in rat granulosa cells by 3',5'-cyclic adenosine monophosphate, activin, and follistatin"Mol-Cell-Endocrinol. 149(1-2). 71-77 (1999)
[Publications] Tano-M: "The effect of follicle-stimulating hormone (FSH) on the expression of FHS receptor in cultured rat granulosa cells"Life-Sci. 64(12). 1063-1069 (1999)
[Publications] Rodien-P: "Evidences for an allelic variant of the human LC/CG receptor rather than a gene duplication: functional comparison of wild-type and variant receptors"J-Chin-Endocrinol-Metab. 83(12). 4431-4434 (1999)
[Publications] Mizutani-T: "Molecular cloning and functional expression of chicken luteinizing hormone receptor"Biochim-Biophys-Acta. 1397(1). 1-8 (1998)
[Publications] Kobayashi,J: "Morphological assessment of the effect of growth hormone (GH) on preantral follicles from from 11-day-old in an in vitro culture system"Biochem Biophys Res Commun. (in press). (2000)
[Publications] T.Minegishi: "A role of insulin-like growth factor I for follicle stimulating hormone receptor (FSH-R) expression in granulosa cells"Biol Reprod. (in press). (2000)
[Publications] Y.Hosoi: "Stimulation of chinese hamster ovary cells expressing human thyrotropin receptors by serum human chorionic gonadotropin of patients with hydatidiform mole"Thyroid. (in press). (2000)
[Publications] T.Hirakawa: "Effect of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on the expression of luteinizing hormone (LH) receptors during cell differentiation in cultured granulosa cells"Arch Biochem Biophys. (in press). (2000)
[Publications] I.Ito: "Presence of activin signal transduction in normal ovarian cells and epithelial ovarian carcinoma"British J Cancer. (in press). (2000)
[Publications] Hirakawa T: "Effect of 2,3,7,8-tetrachlorodibenzo-p-dioxin(TCDD) on the expression of FSH receptors during cell diffentiation in cultured granulosa cells"Endocrinology. (in press). (2000)
[Publications] Ni X: "Activin-A in JEG-3 cells: potential role as an autocrine regulator of steroidogenesis"Biol Reprod. (in press). (2000)
[Publications] T.Minegishi: "The mechanisms of retinoic acid-induced regulation on the follicle -stimulating hormone receptor (FSH-R) in rat granulosa cells"Biochim Biophys Acta. (in press). (2000)
[Publications] 青木宏: "ゴナドトロピン(LH/FSH)による性ステロイド合成の制御リコンビナントゴナドトロピンを用いた実験成績から-"産科と婦人科. 65(3). 309-316 (1998)
[Publications] 土屋恵: "ovarian-remnant syndrome(卵巣レムナント症候群)"診断と治療. 86/増刊号. 464 (1998)
[Publications] 平川隆史: "polycystic ovary syndrome(PCOS)(多嚢胞性卵巣症候群)"診断と治療. 86/増刊号. 469 (1998)
[Publications] 金井真理: "resistant ovary syndrome(ROS)(無反応性卵巣症候群)"診断と治療. 86/増刊号. 479 (1998)
[Publications] 亀田高志: "Stein-Leventhal syndrome"診断と治療. 86/増刊号. 489 (1998)
[Publications] 峯岸敬: "アクチビン"HORMONE FRONTIER IN GYNECOLOGY. 6(3). 194-197 (1999)
[Publications] 伊吹令人: "最適排卵法の確立"平成9年度厚生省心身障害研究報告書. 144-160 (1998)
[Publications] 安部由美子: "インヒビン、アクチビン、フォリスタチン"生殖内分泌分科会NEWSLETTER. No.3. 12-13 (1998)
[Publications] 安部由美子: "妊娠とアクチビン、インヒビン"Hormone Frontier in Gynecology. 5(1). 63-71 (1998)
[Publications] 峯岸敬: "生殖とホルモン:ゴナドトロピン受容体(日本比較内分泌学会編)"学会出版センター. 224 (1998)
[Publications] 峯岸敬: "検査の診断効率とピットフォール:LH,FSH(編集代表中井利昭、編集吉田浩、下条文武、奈良信雄、野村文夫)"中外医学社. 419 (1998)
[Publications] Mizunuma,H: "Frontiers in Endocrinology vol.21 Ovarian Function Research"Serono Symposia Publications. 7 (1999)
[Publications] 安部由美子: "産婦人科の世界第50巻冬季増刊号卵巣-機能と病態生理- インヒビン、アクチビン、フォリスタチン"医学の世界社. 68-76 (1998)
[Publications] 安部由美子: "新女性医学大系12排卵と月経武谷雄二総編集、青野敏博、麻生武志、中野仁雄、野澤志朗編集、岡村均担当編集インヒビン、アクチビン、フォリスタチン"中山書店(東京). 18 (1998)

1999 Fiscal Year Annual Research Report

インヒビン/アクチビンファミリーの作用解析による単一排卵機序の探索

Principal Investigator

伊吹 令人 群馬大学, 医学部, 教授 (40008256)

Research Products

[Publications] Hirakawa-T: "Effect of prolactin on the expression of luteinizing hormone receptors during cell differentiation in cultured rat granulosa cells"Endocrinology. 140(8). 3444-3451 (1999)

[Publications] Tsuchiya-M: "Control of expression of luteinizing hormone receptor by local factors in rat granulosa calls"Arch-Biochem-Biophys. 367(2). 185-192 (1999)

[Publications] Liu-X: "A comparative study on transforming growth factor-beta and activin A for immature mice. Preantral follicles from adult, immature, and diethylstilbestrol-primed immature mice"Endocrinology. 140(6). 2480-2485 (1999)

[Publications] Kameda-T: "Regulation of cAMP responsive element binding modulator isoforms in cultured rat ovarian granulosa cells"Biochim-Biophys-Acta. 1445(1). 31-38 (1999)

[Publications] Michishita-M: "Expression of adrenomedullin in the endometrium of the human uterus"Obstet-Gynecol. 93(1). 66-70 (1999)

[Publications] Mizunuma-H: "Activin from secondary follicles causes small preantral follicles to remain dormant at the resting stage"Ecdocrinology. 140(1). 37-42 (1999)

[Publications] Kamijo-T: "Biochemical evidence for autocrine/paracrine regulation of apoptosis in cultured uterine epithelial cells during mouse embryo implantation in vitro"Mol-Hum-Reprod. 4(10). 990-998 (1998)

[Publications] Abe-K: "Expression and effect of adrenomedullin on rat granulosa cell"Endocrinology. 139(12). 5263-5266 (1998)

[Publications] Liu-X: "Effects of growth hormone, activin, and follistatin on the development of preantral follicle from immature female mice"Endocrinology. 139(5). 2342-2347 (1998)

[Publications] Kishi-H: "The effect of activin and FSH on the differentiation of rat granulosa cells"FEBS-Lett. 422(2). 274-278 (1998)

[Publications] Minegishi-T: "Control of FSH receptor mRNA expression in rat granulosa cells by 3',5'-cyclic adenosine monophosphate, activin, and follistatin"Mol-Cell-Endocrinol. 149(1-2). 71-77 (1999)

[Publications] Tano-M: "The effect of follicle-stimulating hormone (FSH) on the expression of FHS receptor in cultured rat granulosa cells"Life-Sci. 64(12). 1063-1069 (1999)

[Publications] Rodien-P: "Evidences for an allelic variant of the human LC/CG receptor rather than a gene duplication: functional comparison of wild-type and variant receptors"J-Chin-Endocrinol-Metab. 83(12). 4431-4434 (1999)

[Publications] Mizutani-T: "Molecular cloning and functional expression of chicken luteinizing hormone receptor"Biochim-Biophys-Acta. 1397(1). 1-8 (1998)

[Publications] Kobayashi,J: "Morphological assessment of the effect of growth hormone (GH) on preantral follicles from from 11-day-old in an in vitro culture system"Biochem Biophys Res Commun. (in press). (2000)

[Publications] T.Minegishi: "A role of insulin-like growth factor I for follicle stimulating hormone receptor (FSH-R) expression in granulosa cells"Biol Reprod. (in press). (2000)

[Publications] Y.Hosoi: "Stimulation of chinese hamster ovary cells expressing human thyrotropin receptors by serum human chorionic gonadotropin of patients with hydatidiform mole"Thyroid. (in press). (2000)

[Publications] T.Hirakawa: "Effect of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on the expression of luteinizing hormone (LH) receptors during cell differentiation in cultured granulosa cells"Arch Biochem Biophys. (in press). (2000)

[Publications] I.Ito: "Presence of activin signal transduction in normal ovarian cells and epithelial ovarian carcinoma"British J Cancer. (in press). (2000)

[Publications] Hirakawa T: "Effect of 2,3,7,8-tetrachlorodibenzo-p-dioxin(TCDD) on the expression of FSH receptors during cell diffentiation in cultured granulosa cells"Endocrinology. (in press). (2000)

[Publications] Ni X: "Activin-A in JEG-3 cells: potential role as an autocrine regulator of steroidogenesis"Biol Reprod. (in press). (2000)

[Publications] T.Minegishi: "The mechanisms of retinoic acid-induced regulation on the follicle -stimulating hormone receptor (FSH-R) in rat granulosa cells"Biochim Biophys Acta. (in press). (2000)

[Publications] 青木 宏: "ゴナドトロピン(LH/FSH)による性ステロイド合成の制御 リコンビナントゴナドトロピンを用いた実験成績から-"産科と婦人科. 65(3). 309-316 (1998)

[Publications] 土屋 恵: "ovarian-remnant syndrome(卵巣レムナント症候群)"診断と治療. 86/増刊号. 464 (1998)

[Publications] 平川隆史: "polycystic ovary syndrome(PCOS)(多嚢胞性卵巣症候群)"診断と治療. 86/増刊号. 469 (1998)

[Publications] 金井真理: "resistant ovary syndrome(ROS)(無反応性卵巣症候群)"診断と治療. 86/増刊号. 479 (1998)

[Publications] 亀田高志: "Stein-Leventhal syndrome"診断と治療. 86/増刊号. 489 (1998)

[Publications] 峯岸 敬: "アクチビン"HORMONE FRONTIER IN GYNECOLOGY. 6(3). 194-197 (1999)

[Publications] 伊吹令人: "最適排卵法の確立"平成9年度厚生省心身障害研究報告書. 144-160 (1998)

[Publications] 安部由美子: "インヒビン、アクチビン、フォリスタチン"生殖内分泌分科会NEWSLETTER. No.3. 12-13 (1998)

[Publications] 安部由美子: "妊娠とアクチビン、インヒビン"Hormone Frontier in Gynecology. 5(1). 63-71 (1998)

[Publications] 峯岸敬: "生殖とホルモン:ゴナドトロピン受容体(日本比較内分泌学会編)"学会出版センター. 224 (1998)

[Publications] 峯岸敬: "検査の診断効率とピットフォール:LH,FSH(編集代表 中井利昭、編集 吉田 浩、下条文武、奈良信雄、野村文夫)"中外医学社. 419 (1998)

[Publications] Mizunuma,H: "Frontiers in Endocrinology vol.21 Ovarian Function Research"Serono Symposia Publications. 7 (1999)

[Publications] 安部由美子: "産婦人科の世界 第50巻 冬季増刊号 卵巣-機能と病態生理- インヒビン、アクチビン、フォリスタチン"医学の世界社. 68-76 (1998)

[Publications] 安部由美子: "新女性医学大系12排卵と月経 武谷雄二総編集、青野敏博、麻生武志、中野仁雄、野澤志朗編集、岡村均担当編集 インヒビン、アクチビン、フォリスタチン"中山書店(東京). 18 (1998)

伊吹令人群馬大学, 医学部, 教授 (40008256)

[Publications] 青木宏: "ゴナドトロピン(LH/FSH)による性ステロイド合成の制御リコンビナントゴナドトロピンを用いた実験成績から-"産科と婦人科. 65(3). 309-316 (1998)

[Publications] 土屋恵: "ovarian-remnant syndrome(卵巣レムナント症候群)"診断と治療. 86/増刊号. 464 (1998)

[Publications] 峯岸敬: "アクチビン"HORMONE FRONTIER IN GYNECOLOGY. 6(3). 194-197 (1999)

[Publications] 峯岸敬: "検査の診断効率とピットフォール:LH,FSH(編集代表中井利昭、編集吉田浩、下条文武、奈良信雄、野村文夫)"中外医学社. 419 (1998)

[Publications] 安部由美子: "産婦人科の世界第50巻冬季増刊号卵巣-機能と病態生理- インヒビン、アクチビン、フォリスタチン"医学の世界社. 68-76 (1998)

[Publications] 安部由美子: "新女性医学大系12排卵と月経武谷雄二総編集、青野敏博、麻生武志、中野仁雄、野澤志朗編集、岡村均担当編集インヒビン、アクチビン、フォリスタチン"中山書店(東京). 18 (1998)