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Elucidation of mechanisms on the sex differentiation gene family and its mutual regulation

Research Project

Project/Area Number 15390510
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Obstetrics and gynecology
Research InstitutionKobe University (2004-2005)
Kitasato University (2003)

Principal Investigator

HOSHI Nobuhiko  Kobe University, Faculty of Agriculture, Professor, 農学部, 教授 (10209223)

Co-Investigator(Kenkyū-buntansha) SUGAWARA Teruo  Hokkaido University, School of Medicine, Assistant Professor, 医学部, 助手 (40250451)
長谷川 喜久  北里大学, 獣医畜産学部, 教授 (40092001)
Project Period (FY) 2003 – 2005
Project Status Completed (Fiscal Year 2005)
Budget Amount *help
¥16,600,000 (Direct Cost: ¥16,600,000)
Fiscal Year 2005: ¥2,700,000 (Direct Cost: ¥2,700,000)
Fiscal Year 2004: ¥2,600,000 (Direct Cost: ¥2,600,000)
Fiscal Year 2003: ¥11,300,000 (Direct Cost: ¥11,300,000)
KeywordsSex differentiation / Sexual dimorphism / StAR / GnRH / hpg mouse / Apoptosis / SEP / Ad4BP / SF-1 / 性的二型核 / SDN-POA / AVPvN-POA / GrRH / 神経細胞 / SCN / Fosファミリー / アポトーシス制御機構 / Bcl-2ファミリー / Bax / 内分泌攪乱物質 / 性分化 / ダイオキシン(TCDD) / 視床下部-下垂体-性腺系 / DEHP / BPA
Research Abstract

Gonadotropin-deficient (hpg) mice lacking GnRH caused by a deletional mutation of at least 33.5kb encompassing the distal half of GnRH and GAP have infantile reproductive systems and levels of pituitary gonadotropins that are significantly lower than normal. Although activin accelerates synthesis and secretion of FSH in vitro, it has been difficult to investigate the role of activin alone under the influence of GnRH in vivo. The present study was designed to examination whether administration of activin alone would affect gonadotropin production and gonadal development in adult hpg mice. It is clear from the present findings that inferences of activin treatment in the hpg mice under the exception of GnRH increased gonadotropin production, and activated gonadal function. SPB binds StAR protein in cells and enhances the ability of StAR protein to promote syntheses of steroid hormones. Sp1 interacts with Ad4BP/SF-1 and that Sp1 enhances Ad4BP/SF-1-DNA complex formation to regulate human StAR transcription. The hypothalamo-pituitary control of gonadotropin secretion may be affected by the smaller doses of estrogenic agents than the reproductive organs. Furthermore, the fertility rate in the male mice exposed to this estrogenic agent was closely correlated with the testosterone levels, and even more so with the rate-limiting factor of steroidogenesis, StAR gene. Morphological changes in neuronal and astroglial cells occur in the SCN with aging in a sex-specific manner with apoptosis. The sex differences in GnRH releasing function are depend on the sex differences in the activation of GnRH neurons. There is the relationship between the activation of GnRH neurons and that of the cells in AVPvN-POA. From above results, we showed a part of sex differentiation cascade with a focus on StAR gene and the differentiation of gonad, and molecular mechanism of estrogen action to the brain.

Report

(4 results)
  • 2005 Annual Research Report   Final Research Report Summary
  • 2004 Annual Research Report
  • 2003 Annual Research Report
  • Research Products

    (37 results)

All 2006 2005 2004 2003 Other

All Journal Article (29 results) Book (2 results) Publications (6 results)

  • [Journal Article] Both N-terminal and C-terminal regions of steroid sulphatase are important for enzyme activity.2006

    • Author(s)
      Sugawara T
    • Journal Title

      Journal of Endocrinology 188

      Pages: 365-374

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Impaired growth of pancreatic exocrine cells in transgenic mice expressing human activin betaE subunit.2006

    • Author(s)
      Hashimoto O
    • Journal Title

      Biochemical and Biophysical Research Communications 341

      Pages: 416-424

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Cellular defferentiation to M cells in response to bacterial colonization on the follicle-associated epithelium of Peyer's patch in rat small intestine.2006

    • Author(s)
      Chin K
    • Journal Title

      Journal of Veterinary Medical Science (accepted)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Progression of the dose-related effects of estrogenic endocrine disruptors, an important factor in declining fertility, differs between the hypothalamo-pituitary and reproductive organs of male mice.2006

    • Author(s)
      Warita K
    • Journal Title

      Journal of Veterinary Medical Science (accepted)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Both N-terminal and C-terminal regions of steroid sulfatase are important for enzyme activity2006

    • Author(s)
      Sugawara, T
    • Journal Title

      Journal of Endocrinology 188

      Pages: 365-374

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Impaired growth of pancreatic exocrine cells in transgenic mice expressing human activin betaE subunit2006

    • Author(s)
      Hashimoto, O
    • Journal Title

      Biochemical and Biophysical Research Communications 341

      Pages: 416-424

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Molecular cytogenetic aspects of sex differentiation anomalies in the field of obstetrics and gynecology2006

    • Author(s)
      Hoshi, N
    • Journal Title

      Perspectives in Human Genetics, India (in print)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Progression of the dose-related effects of estrogenic endocrine disruptors, an important factor in declining fertility, differs between the hypothalamo-pituitary and reproductive organs of male mice2006

    • Author(s)
      Warita. K
    • Journal Title

      Journal of Veterinary Medical Science (accepted)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Cellular differentiation to M cells in response to bacterial colonization on the follicle-associated epithelium of Peyer's patch in rat small intestine.2006

    • Author(s)
      Chin K
    • Journal Title

      Journal of Veterinary Medical Science (accepted)

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Both N-terminal and C-terminal regions of steroid. sulphatase are important for enzyme activity.2006

    • Author(s)
      Sugawara T
    • Journal Title

      Journal of Endocrinology 188

      Pages: 365-374

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Age-related change and its sex differences in histoarchitecture of the hypothalamic suprachiasmatic nucleus of F344/N rats.2005

    • Author(s)
      Tsukahara S
    • Journal Title

      Experimental Gerontology 475

      Pages: 177-187

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Annual Research Report 2005 Final Research Report Summary
  • [Journal Article] Age-related change and its sex differences in histoarchitecture of the hypothalamic suprachiasmatic nucleus of F344/N rat2005

    • Author(s)
      Tsukahara, S
    • Journal Title

      Experimental Gerontology 40

      Pages: 147-155

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Molecular cytogenetic aspects of sex differentiation anomalies in the field of obstetrics and gynecology.2005

    • Author(s)
      Hoshi N
    • Journal Title

      Perspectives in Human Genetics (accepted)

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Age-related change and its sex differences in histoarchitecture of the hypothalamic suprachiasmatic nucleus of F344/N rats.2005

    • Author(s)
      Tsukahara S
    • Journal Title

      Experimental Gerontology (in press)

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Familial 15p tetrasomy due to extra supernumerary maker 15 chromosome associated with Robertsonian translocation between chromosomes 13 and 14.2004

    • Author(s)
      Hoshi N
    • Journal Title

      Chromosome Science 78・2

      Pages: 7-13

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Role of StAR binding protein in steroidogenic cells.2004

    • Author(s)
      Sugawara T
    • Journal Title

      Endocrinological Research 30・4

      Pages: 695-695

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary 2004 Annual Research Report
  • [Journal Article] Characterization of binding between SF-1 and Sp1 : predominant interaction of SF-1 with the N-terminal region of Spl.2004

    • Author(s)
      Sugawara T
    • Journal Title

      Journal of Endocrinological Investigation 27・2

      Pages: 133-141

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Active isoforms signal through tipe I receptor serine/threonine kinase ALK7.2004

    • Author(s)
      Tsuchida K
    • Journal Title

      Molucular and Cellular Endocrinology 220

      Pages: 59-65

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Familial 15p tetrasomy due to extra supernumerary marker 15 chromosome associated with Robertsonian translocation between chromosomes 13 and 142004

    • Author(s)
      Hoshi, N
    • Journal Title

      Chromosome Science 7

      Pages: 7-13

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Characterization of binding between SF-1 and Sp1 : Predominant interaction of SF-1 with the N-terminal region of Sp12004

    • Author(s)
      Sugawara, T
    • Journal Title

      Journal of Endocrinological Investigation 27

      Pages: 133-141

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Role of StAR binding protein in steroidogenic cells2004

    • Author(s)
      Sugawara, T
    • Journal Title

      Endocrine Research 30

      Pages: 695-695

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Activin isoforms signal through type I receptor serine/threonine kinase ALK7.2004

    • Author(s)
      Tsuchida, K
    • Journal Title

      Molecular and Cellular Endocrinology 220

      Pages: 59-65

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Familial 15p tetrasomy due to extra supernumerary marker 15 chromosome associated with Robertsonian translocation between chromosomes 13 and 14.2004

    • Author(s)
      Hoshi N
    • Journal Title

      Chromosome Science 78・2

      Pages: 7-13

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Characterization of binding between SF-1 and Sp1 : predominant interaction ofSF-1 with the N-terminal region of Sp1.2004

    • Author(s)
      Sugawara T
    • Journal Title

      Journal of Endocrinological Investigation 27・2

      Pages: 133-141

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Maternal serum markers in pregnancies associated with fetal trismoy 21 of native Japanese women with or without fetal morphological abnormalities.2003

    • Author(s)
      Hoshi N
    • Journal Title

      The Hokkaido Journal of Medical Science 78・2

      Pages: 139-145

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Steroidogenic acute regulatory protein-binding protein cloned by a teast two-hybrid system.2003

    • Author(s)
      Sugawara T
    • Journal Title

      The Journal of Biological Chemistry, 278・43

      Pages: 42487-42494

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Cytogenetic analysis of uterine leiomyoma : the size, histopathology and GnRHa-response in relation to chromosonie karyotype2003

    • Author(s)
      Kataoka, S
    • Journal Title

      European Journal of Obstetrics & Gynecology and Reproductive Biology 110

      Pages: 58-62

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Steroidogenic acute regulatory protein-binding protein cloned by a yeast two-hybrid system2003

    • Author(s)
      Sugawara, T
    • Journal Title

      The Journal of Biological Chemistry 278

      Pages: 42487-42494

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Maternal serum markers in pregnancies associated with fetal trisomy 21 of native Japanese women with or without fetal morphological abnormalities2003

    • Author(s)
      Hoshi, N
    • Journal Title

      The Hokkaido Journal of Medical Science 78

      Pages: 139-145

    • NAID

      110000339788

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Book] Perspectives in Human Genetics2006

    • Author(s)
      Hoshi N
    • Publisher
      Molecular cytogenetic aspects of sex differentiation anomaliesin the field of obstetrics and gynecology. (in print)
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Book] Perspectives in Human Genetics(Molecular cytogenetic aspects of sex differentiation anomalies in the field of obstetrics and gynecology)2006

    • Author(s)
      Hoshi N
    • Publisher
      (in press)
    • Related Report
      2005 Annual Research Report
  • [Publications] Hoshi N: "Familial 15p tetrasomy due to extra supernumerary marker 15 chromosome associated with Robertsonian translocation between chromosomes 13 and 14."Chromosome Science. (accepted). (2004)

    • Related Report
      2003 Annual Research Report
  • [Publications] Hoshi N: "Maternal serum markers in pregnancies associated with fetal trisomy 21 of native Japanese women with or without fetal morphological abnormalities."Hokkaido J Med Sci. 78・2. 139-145 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Hoshi N: "Molecular cytogenetic aspects of sex differentiation anomalies in the field of obstetrics and gynecology."Perspectives in Human Genetics. (accepted). (2004)

    • Related Report
      2003 Annual Research Report
  • [Publications] Kataoka S: "Cytogenetic analysis of uterine leiomyoma : the size, histopathology and GnRHa-response in relation to chromosome karyotype."European Journal of Obstetrics & Gynecology and Reproductive Biology.. 110・1. 56-62 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Sugawara T: "Steroidogenic acute regulatory protein-binding protein cloned by a yeast two-hybrid system."JBC. 278・43. 42487-42494 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Sugawara T: "The potential function of steroid sulfatase activity in steroid production and steroidogenic acute regulatory protein expression."Biochem J. (In print). (2004)

    • Related Report
      2003 Annual Research Report

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Published: 2003-04-01   Modified: 2016-04-21  

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