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Mechanism underlying the regulation of apoptosis in female reproductive cells

Research Project

Project/Area Number 10470346
Research Category

Grant-in-Aid for Scientific Research (B).

Allocation TypeSingle-year Grants
Section一般
Research Field Obstetrics and gynecology
Research InstitutionKobe University

Principal Investigator

MARUO Takeshi  School of Medicine, Kobe University Professor, 医学部, 教授 (60135811)

Co-Investigator(Kenkyū-buntansha) NAKAGO Satoshi  Unversity Hospital, Kobe University Assistant Professor, 医学部・附属病院, 助手 (50283891)
TAKEKIDA Shigeki  School of Medicine, Kobe University Assistant Professor, 医学部・附属病院, 助手 (60324927)
SATO Asomi  Unversity Hospital, Kobe University Assistant Professor, 医学部・附属病院, 助手 (90314484)
MATSUO Hiroya  Unversity Hospital, Kobe University Associate Professor, 医学部・附属病院, 助教授 (60229432)
吉田 茂樹  神戸大学, 医学部, 助手 (70294212)
佐本 崇  神戸大学, 医学部, 助手 (80294213)
大谷 徹郎  神戸大学, 医学部・附属病院, 助教授 (50203823)
Project Period (FY) 1998 – 2000
Project Status Completed (Fiscal Year 2000)
Budget Amount *help
¥9,300,000 (Direct Cost: ¥9,300,000)
Fiscal Year 2000: ¥1,500,000 (Direct Cost: ¥1,500,000)
Fiscal Year 1999: ¥1,300,000 (Direct Cost: ¥1,300,000)
Fiscal Year 1998: ¥6,500,000 (Direct Cost: ¥6,500,000)
Keywordsleiomyoma cell / progesterone / EGF / Bcl-2 / granulosa cell / apoptosis / Fas / PCNA / adrenomedullin / レボノルゲストレル / IUS / 子宮内膜細胞 / 子宮頚部扁平上皮 / CDDP / Fas ligand / テロメラーゼ / 胎盤 / 絨毛外栄養膜細胞 / TNFα
Research Abstract

1) Sex steroidal regulation of leiomyoma growth and apoptosis.
Progesterone up-regulates the PCNA protein expression in cultured leiomyoma cells. Consistently, the PCNA labeling index in leiomyoma tissues predominated in the secretory, progesterone-dominated, phase of the menstrual cycle, compared to that in the proliferative phase. Furthermore, we demonstrated that EGF-like protein expression in cultured leiomyoma cells was up-regulated by progesterone, whereas EGF receptor expression in those cells was up-regulated by 17β-estradiol. We have also demostrated a greater abundance of Bcl-2 protein in leiomyomas, relative to the normal myometrium of the same individual uterus, and that Bcl-2 protein expression in leiomyoma cells predominated in the secretory, progesterone-dominated phase of the menstrual cycle, compared to that in the proliferative phase. The abundant expression of Bcl-2 protein in leiomyoma may be one of the molecular bases for the enhanced growth of leiomyoma, relative t … More o that of normal myometrium, in the uterus.
2) Granulosa cell proliferation and apoptosis during follicular growth and regression
We examined the proliferative activity of granulosa cells during follicular growth and regression on the basis of PCNA expression. The PCNA expression was augmented by FSH in a dose-dependent manner. FSH, IGF-I and EGF acted as up-regulators of the proliferative activty of granulosa cells, whereas TNFα and TGFβ acted as down-regulators of granulosa cell proliferation. Analysis of DNA 3'-end labeling and Fas antigen and its ligand expression in the ovary suggested that apoptosis in atretic primordial and preantral follicles first occurred in the oocyte, whereas apoptosis in atretic antral follicles first occurred in the granulosa cells. Futhermore, we noted that FSH and IGF-I inhibited apoptosis of granulosa cells, whereas TGFβ and TNFα stimulated apoptosis of the cells. These results suggest that dominant exposure to follicle survival factors such as FSH, IGF-I and EGF may be responsible for the selection of growing follicles, while dominant exposure to atretogenic factors such as TGFβ and TNFα may be responsible for follicle atresia. Less

Report

(4 results)
  • 2000 Annual Research Report   Final Research Report Summary
  • 1999 Annual Research Report
  • 1998 Annual Research Report
  • Research Products

    (39 results)

All Other

All Publications (39 results)

  • [Publications] Peng X,Maruo T,Matsuo H,Takekida S.Deguchi J: "Serum deprivation-induced apoptosis in cultured porcine granulosa cell is characterized by increased expression cl p53 protein,Fas antigen and Fas igand and by decreased expression cl PCNA."Endocrine Journal. 45. 247-253 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Shimomura Y,Matsuo H,Samoto T.Maruo T: "Up-regulation by progesterone of proliferating cell nuclear antigen and epidermal growth factor expression in human uterine leiomyoma."J Clin Endocrinol Metab. 83. 2192-2198 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Maruo T,Laoag-Fernandez JB.Takekida S,Peng X,Deguchi J.Samoto T,Kondo H,Matsuo H: "Regulation of granulosa cell proliferation and apoptosis during follicular development."Gynecol Endocrinology. 13. 410-419 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Matsuo H,Kurachi O,Shimomura Y,Samoto T,Maruo T: "Molecular bases for the actions of ovarian sex steroids in the regulation of proliferation and apoptosis of human uterine leiomyoma."Oncology. 57. 49-58 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Takekida S,Deguchi J,Samoto T,Matsuo H,Maruo T: "Comparative analysis of the effects of gonadotropin-releasing hormone agonist on the proliferative acitivity, apoptosis, and steroidogenesis in cultured porcine granulosa cells at varying stages of follicular growth."Endocrine. 12. 61-67 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Moriyama T,Otani T,Maruo T: "Expression of adrenomedullin by human granulosa lutein cells and its effect on progesterone production."Eur J of Endocrinol. 142. 671-676 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Maruo T,Matsuo H,Samoto T,Shimomura Y: "Sex steroidal regulation of leiomyoma growth and apoptosis."Pathogenesis and Medical Management of Uterine Fibroids, Parthenon Publishing, Lancs,U.K., (eds.Brosens I, Lunenfeld B, Donnez J). 16 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Maruo T,Takekida S,Peng X,Deguchi J,Samoto T,Kondo H,Matsuo H: "Granulosa cell proliferation and apoptosis during follicular growth and regression."Ovarian Function Research : Present and Future (Frontiers in Endocrinology), Serono Symposia Publications, Rome, (eds.Fujimoto S, Adashi EY.Hsueh AJW, Strauss JF). 7 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Peng X, Maruo T, Matsuo H, Takekida S, Deguchi J: "Serum deprivation-induced apoptosis in cultured poreine granulosa cells is characterized by increased expression of p53 protein, Fas antigen and Fas ligand and by decreased expression of PCNA."Endocrine Journal. 45. 247-253 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Shimomura Y, Matsuo H, Samoto T, Maruo T: "Up-regulation by progesterone of proliferating cell nuclear antigen and epidermal growth factor expression in human uterine leiomyoma."J Clin Endoerinol Metab. 83. 2192-2198 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Maruo T, Laoag-Fernandez JB, Takekida S, Peng X, Deguchi J, Samoto T, Kondo H, Matsuo H: "Regulation of granulosa cell proliferation and apoptosis during follicular development."Gyneeol Endocrinology. 13. 410-419 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Matsuo H, Kurachi O, Shimomura Y, Samoto T, Maruo T: "Molecular bases for the actions of ovarian sex steroids in the regulation of proliferation and apoptosis of human uterine leiomyoma."Oncology. 57. 49-58 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Takekida S, Deguchi J, Samoto T, Matsuo H, Maruo T: "Comparative analysis of the effects of gonadotropin-releasing hormone agonist on the proliferative acitivity, apoptosis, and steroidogenesis in cultured porcine granulosa cells at varying stages of follicular growth."Endocrine. 12. 61-67 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Moriyama T, Otani T, Maruo T: "Expression of adrenomedullin by human granulosa lutein cells and its effect on progesterone production."Eur J of Endocrinology. 142. 671-676 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Maruo T, Matsuo H, Samoto T, Shimomura Y (eds. Brosens I, Lunenfeld B, Donnez J): "Sex steroidal regulation of leiomyoma growth and apoptosis."In : Pathogenesis and Medical Management of Uterine Fibroids, Parthenon Publishing, Lancs, U.K.. 17-32 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Maruo T, Takekida S, Peng X, Deguchi J, Samoto T, Kondo H, Matsuo H (eds. Fujimoto S, Adashi EY, Hsueh AJW, Strauss JF): "Granulosa cell proliferation and apoptosis during follicular growth and regression."In : Ovarian Function Research : Present and Future (Frontiers in Endocrinology), Serono Symposia Publications, Rome. 179-185 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Maruo T: "Usefulness of estradiol/progesterone releasing vaginal rings in long-term management of postmenopausal women."Adv Obstet Gynecol. 52. 266-271 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Takekida S: "Comparative analysis of the effects of gonadotropin-releasing hormone agonist on the proliferative activity, apoptosis, and steroidogenesis in cultured porcine granulosa cells at varying stages of follicular growth."Endocrine. 12. 61-67 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Moriyama T: "Expression of adrenomedullin by human granulosa lutein cells and its effect on progesterone production."Eur J of Endocrinol. 142. 671-676 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Ishihara N: "Changes in proliferative potential, apoptosis and Bcl-2 protein expression in cytotrophoblasts and svncytiotrophoblast in human placenta over the course of pregnancy."Endocrine J. 47. 317-327 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Maruo T,: "Levonorgestrel-releasing IUDs in the long-term management of menorrhagia."J Obstet Gynaecol Res. 26. 75-75 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Laoag-Fernandez JB: "Adrenomedullin expression in the human endometrium."Endocrine. 12. 15-19 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Maruo T,: "Estradiol/progesterone releasing vaginal rings for hormone replacement therapy in postmenopausal women."Menopause, Monduzzi Editore, Bologna, Italy (eds.Aso T,Yanaihara T,Takelani Y,Suda T,Tanaka H.Maehara S). 5 (1999)

    • Related Report
      2000 Annual Research Report
  • [Publications] 丸尾猛: "避妊法の実際-IUD-薬剤付加型IUD プロゲスチン徐放型IUD"産科と婦人科「避妊-女性のwell-beingをめざして」産科と婦人科2000年増刊,診断と治療社(丸尾猛 編). 5 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Takeuchi S.Ishihara N.Maruo T.et,al.: "Stromal leydig cell turmor of the ovary.Case repert and literature review"Int J Gynecol Pathl. 18. 178-182 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Maruo T.Samoto T.Yoshida S.Matsuo H.et,al.: "Estradiol / progesterone-releasing vaginal rings for hormone replacement therapy in postmenopansal woman"Climacteric. 2. 100-100 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Matsuo H.Kurachi O.Shimomura Y.Maruo T.et,al.: "Molecular bases for the actions of ovarian sex steroids in the regulation of proliferation and apoptosis of human uterine leiomyoma"Oncology. 57. 49-58 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Nakago S.Funakoshi T.Maruo T.et,al.: "Regulation of circulating levels of IGF-I in pregnant rats: changes in nitrogen balance correspond with changes in serum IGF-I concentrations"J Endocrinol. 163. 373-377 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Maruo T.: "Expression of Squamous Cell Carcinoma (SCC) Antigen in uterine cervical carcinoma and its treatment response"The proceeding's of Seoul Symposium on Gynecologic Oncology. 61-72 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Maruo T,Matsuo H et.al.(eds Brosen I.Lunenfeld B): "Sex steroidal regulation of leiomyoma growth and apoptosis In: Pathogenesis and Medical Management of Uterine Fibroids"Parthenon Publishing,Lancs,U.K.. 16 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Maruo T,Matsuo H et.al.(eds.Coutinho EM.Spinola P): "Regulation of proliferation and apoptosis of uterine myometria and leiomyoma by sex steroid hormones In: Reproductive Medicine"Parthenon Publishing,Lancs,U.K.. 10 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Peng X. Maruo T. Matsue H. Takekida S.: "Serum deprivation-induced apoptosis in cultured porcine granulosa cells is characterized by increased expression of p53 protein.Fas antigen and Fas ligand and by decreased expression of PCNA" Endocrine Journal. 45巻. 247-253 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Liu L. Yamabe S. Maruo T.: "Comparison of the efficacy of luteinizing hormone and human choripnic gonadotropin for ovulation induction and corpus luteum formation in gonadotropin-primed imnature rats" Jpn J Fertil Steril. 43巻. (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Shimomura Y. Moriyama T. Funakeshi T. Maruo T.: "Up-regulation by progesterone of proliterating cell nuclear antigen and epidermal growth factor expression in human uterine leiomyoma" J Clin Endocrinol Metab. 83巻. 2192-2198 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Mochizuki M. Maruo T. Matsuo H. Samoto T.: "Biology of human trophoblast" International J Obst Gynecol. 60巻. S21-S28 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Maruo T. Yoshida S. Samoto T. Tateiwa Y.: "Factors regulating SCC antigen expression in squanious cell carcinoma of the uterine cervix" Tomor Biology. 19巻. 494-504 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Maruo T. Laoag-Fernenlez J. Takekida S. Peng X.: "Regulation of granulosa cell proliferation and apoptosis during follicular development" Gynecol Endocrinology. (in press).

    • Related Report
      1998 Annual Research Report
  • [Publications] Funakoshi T. Maruo T. et al.leds.Nakayama T. Makino T.: "Insulin-like growth factor-I(IGF-I)and IGF binding protein(IGFBPs)in fetal developement.In:Biology of Pregnancy" Keiseisha,Tokyo, 48-62 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] 丸尾 猛(吉村泰典 編): "卵胞発育と閉鎖-成長因子- In:卵巣:機能と病態生理" 医学の世界社, 57-67 (1999)

    • Related Report
      1998 Annual Research Report

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Published: 1998-04-01   Modified: 2016-04-21  

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