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膜結合型ペプチダーゼ阻害剤ベスタチンの卵胞発育促進作用の解析

Research Project

Project/Area Number 13671709
Research Category

Grant-in-Aid for Scientific Research (C)

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

Principal Investigator

YOSHIOKA Shinya  Kyoto University, Graduate school of medicine, Assistant, 医学研究科, 助手 (90333575)

Co-Investigator(Kenkyū-buntansha) FUJIWARA Hiroshi  Kyoto University, Graduate school of medicine, Lecturer, 医学研究科, 講師 (30252456)
TATSUMI Keiji  Kyoto University, Graduate school of medicine, Assistant, 医学研究科, 助手 (10324633)
Project Period (FY) 2001 – 2002
Project Status Completed (Fiscal Year 2002)
Budget Amount *help
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2002: ¥1,600,000 (Direct Cost: ¥1,600,000)
Fiscal Year 2001: ¥1,900,000 (Direct Cost: ¥1,900,000)
Keywordsinfertility / membrane-bound peptidase / follicle / ovary / granulose cell / theca cell / bioactive peptide
Research Abstract

Ovulation induction is a very important therapy for most infertile women. However, in some cases, gonadotropin therapy, which is widely used as the main therapy for ovulation induction in the world, cannot make the follicles grow in the ovary. In such cases, there are no effective tfierapies so far. Therefore, a new assisted therapy for ovulation induction that locally regulates the effects of gonadotropin is necessary to solve this problem. Although many studies clarified that various peptides such as cytokines and growth factors play important roles as local regulators in folliculogenesis, a new ovulation induction therapy using these peptides has not been established yet. We reported several membrane-bound peptidases are expressed in human follicle and these peptidases are suggested to locally control the ovarian cell functions by regulating the concentration of bioactive peptides. In addition, the study using inhibitors of these peptidases implied that they regulate the effects of gonadotropin locally. In this study, we examined the effects of bestatin, inhibitor of aminopeptidase, in folliculogenesis for the purpose of clinical use. The culture of human or porcine follicles, granulose cells or theca cells showed that bestatin affected folliculogenesis and steroidogenesis of these cells under gonadotropin stimulation. Although the substrates of these membrane-bound peptidase in ovary has not been found, the way of bestatin's effects suggested that bestatin has possibility to be utilized as therapy for polycystic ovary that often causes the ovulation disturbance

Report

(3 results)
  • 2002 Annual Research Report   Final Research Report Summary
  • 2001 Annual Research Report
  • Research Products

    (31 results)

All Other

All Publications (31 results)

  • [Publications] Nakayama T.: "Human peripheral blood mononuclear cells (PBMC) in early pregnancy promote embryo invasion in vitro : HCG enhances the effects of PBMC"Hum. Reprod.. 17. 207-212 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Espey L.L.: "3alpha-hydroxysteroid dehydrogenase messenger RNA transcription in the immature rat ovary in response to an ovulatory dose of gonadotropin"Biol. Reprod.. 65. 72-78 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Egawa H.: "Peripheral blood mononuclear cells in early pregnancy promote invasion of human choriocarcinoma cell line, BeWo cells"Hum. Reprod.. 17. 473-480 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Yoshioka S.: "Gonadotropin-induced expression of pancreatitis-associated protein-III mRNA in the rat ovary at the time of ovulation"J. Endocrinol.. 174. 485-492 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Sato Y.: "Involvement of dipeptidyl peptidase IV in extravillous trophoblas invasion and differentiation"J Clin Endocrinol Metab.. 87. 4287-4296 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Kosaka K.: "Human chorionic gonadotropin (HCG) activates monocytes to produce interleukin-8 via a different pathway from luteinizing hormone/HCG receptor system"J Clin Endocrinol Metab.. 87. 5199-5208 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Fujiwara H.: "Human endometrial epithelial cells express ephrin A1 : possible interaction between human blastocysts and endometrium via Eph-ephrin system"J Clin Endocrinol Metab.. 87. 5801-5807 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Kosaka K.: "Human peripheral blood mononuclear cells enhance cell-cell interaction between human endometrial epithelial cells and BeWo-cell spheroids"Hum. Reprod.. 18. 19-25 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Fujiwara H.: "Acute elevation of plasma D-dimer levels associated with rupture of an ovarian endometriotic cyst : Case report"Hum. Reprod.. 18. 338-341 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Yoshioka S.: "Melanoma cell adhesion molecule (MCAM/CD146) is expressed on human luteinizing granulosa cells : enhancement of its expression by hCG, IL-1 and TNF-α"Mol Hum Reprod.. 9(In Press). (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Higuchi T.: "Cyclic AMP enhances the expression of melanoma cell adhesion molecule in choriocarcinoma cell JEG3 and human chorionic villous explant cultures : a possible involvement in extravillous trophoblast differentiation"Mol Hum Reprod.. 9(In Press). (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Nakayama T.: "Human peripheral blood mononuclear cells (PBMC) in early pregnancy promote embryo invasion in vitro: HCG enhances the effects of PBMC"Hum. Reprod.. 17. 207-212 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Espey L. L.: "3alpha-hydroxysteroid dehydrogenase messenger RNAtranscription in the immaturerat ovaiy in response to an ovulatory dose of gonadotropin"Biol. Reprod.. 65. 272-278 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Egawa H.: "Peripheral blood mononuclear cells in early pregnancy promote invasion of human choriocarcinorna cell line, BeWo cells"Hum. Reprod.. 17. 473-480 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Yoshioka S.: "Gonadotropin-induced expression of pancreatitis-associated protein-III mRNA in (he rat ovary at tfie time of ovulation"J. Endocrinol.. 174. 485-492 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Sato Y.: "Involvement of dipeptidyl peptidase IV in extravillons trophoblast invasion and differentiation"J Clin Endocrinol Metab.. 87. 4287-4296 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Kosaka K.: "Human chorionic gonadotropin (HCG) activates monocytes to produce interleukin-8 via a different pathway from luteinizing hormone/HCG receptor system"J Clin Endocrinol Meteb.. 87. 5199-5208 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Fujiwara H.: "Human endomefrial epithelial cells express ephrin A1: possible interaction between human blastocysts and endometrium via Eph-ephrin system"J Clin Endocrinol Metab.. 87. 5801-5807 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Kosaka K.: "Human peripheral blood mononuclear cells enhance cell-cell interaction between human endometrial epithelial cells and BeWo-cell spheroids"Hum. Reprod.. 18. 473-480 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Fujiwara H.: "Acute elevation of plasma D-dimer levels associated wilh rupture of an ovarian endometriotic cyst: Case report"Hum. Reprad.. 18. 338-341 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Yoshioka S.: "Melanoma cell adhesion molecule (MCAM/CD146) is expressed on human luteinizing granulosa cells:enhancement of its expression by hCG,lL-1 and TNF-alpha"Mol. Hum. Reprod.. 9 (In press). (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Higuchi T.: "Cyclic AMP enhances the expression of melanoma cell adhesion molecule in choriocaicinoma cell JEG3 and human chorionic villous explant cultures: a possible involvement in extraviffous trphoblast differentiation"Mol. Hum. Reprod.. 9 In press. (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Yoshioka S.: "Gonadotropin-induced expression of pancreatitis-associated protein-III mRNA in the rat ovary at the time of ovulation"J. Endocrinol.. 174. 485-492 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Sato Y.: "Involvement of dipeptidyl peptidase IV in extravillous trophoblast invasion and differentiation"J Clin Endocrinol Metab.. 87. 4287-4296 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Kosaka K.: "Human chorionic gonadotropin (HCG) activates monocytes to produce interleukin-8 via a different pathway from luteinizing hormone/HCG receptor system"J Clin Endocrinol Metab.. 87. 5199-5208 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Fujiwara H.: "Human endometrial epithelial cells express ephrin A1 : possible interaction between human blastocysts and endometrium via Eph-ephrin system"J Clin Endocrinol Metab.. 87. 5801-5807 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Kosaka K.: "Human peripheral blood mononuclear cells enhance cell-cell interaction between human endometrial epithelial cells and BeWo-cell spheroids"Hum. Reprod.. 18. 19-25 (2003)

    • Related Report
      2002 Annual Research Report
  • [Publications] Fujiwara H.: "Acute elevation of plasma D-dimer levels associated with rupture of an ovarian endometriotic cyst : Case report"Hum. Reprod.. 18. 338-341 (2003)

    • Related Report
      2002 Annual Research Report
  • [Publications] Nakayama T.: "Human peripheral blood mononuclear cells (PBMC) in early pregnancy promote embryo invasion in vitro: HCG enhances the effects of PBMC"Hum. Reprod.. 17. 207-212 (2002)

    • Related Report
      2001 Annual Research Report
  • [Publications] Espey L.L: "3alplia-hydroxysteroid dehydrogenase messenger RNA transcription in the immature rat ovary in response to an ovulatory dose of gonadotropin"Biol. Reprod.. 65. 72-78 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Egawa H.: "Peripheral blood mononuclear cells in early pregnancy promote invasion of human choriocarcinoma cell line, BeWo cells"Hum. Reprod.. 17. 473-480 (2002)

    • Related Report
      2001 Annual Research Report

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Published: 2001-04-01   Modified: 2016-04-21  

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