2005 Fiscal Year Final Research Report Summary
Elucidation of mechanisms on the sex differentiation gene family and its mutual regulation
| Project/Area Number |
15390510
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Obstetrics and gynecology
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| Research Institution | Kobe University (2004-2005)
Kitasato University (2003) |
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Principal Investigator |
HOSHI Nobuhiko Kobe University, Faculty of Agriculture, Professor, 農学部, 教授 (10209223)
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| Co-Investigator(Kenkyū-buntansha) |
SUGAWARA Teruo Hokkaido University, School of Medicine, Assistant Professor, 医学部, 助手 (40250451)
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| Project Period (FY) |
2003 – 2005
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| Keywords | Sex differentiation / Sexual dimorphism / StAR / GnRH / hpg mouse / Apoptosis / SEP / Ad4BP / SF-1 |
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| 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.
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