| Project/Area Number |
15591731
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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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 | The University of Tokyo |
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Principal Investigator |
YANO Tetsu The University of Tokyo, Faculty of Medicine, Assistant Professor, 医学部附属病院, 助教授 (90251264)
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| Co-Investigator(Kenkyū-buntansha) |
NAKAGAWA Shunsuke The University of Tokyo, Faculty of Medicine, Assistant, 医学部附属病院, 助手 (70270874)
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| Project Period (FY) |
2003 – 2005
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| Project Status |
Completed (Fiscal Year 2005)
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| Budget Amount *help |
¥3,400,000 (Direct Cost: ¥3,400,000)
Fiscal Year 2005: ¥600,000 (Direct Cost: ¥600,000)
Fiscal Year 2004: ¥1,300,000 (Direct Cost: ¥1,300,000)
Fiscal Year 2003: ¥1,500,000 (Direct Cost: ¥1,500,000)
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| Keywords | GnRH analog / GnRH antagonist / GnRH II / ovary / endometrial cancer / endometriosis / apoptosis / cell cycle / 顆粒膜細胞 / フローサイトメトリー / HEC-1 |
|---|
| Research Abstract |
1) GnRH I antagonist, Cetrorelix, directly inhibits the proliferation of HEC-1A human endometrial cancer cell line through mechanisms mediated by GnRH I receptor and involving multiple events in cell-cycle progression, including G2 phase cell cycle arrest coupled with the activation of p53 and the inactivation of cdc2, presumably attributable to an up-regulation of Weel.
2) In light of the anti-proliferative and anti-inflammatory effects of GnRH II on endometriotic stromal cells (ESC), the lower expression of GnRH II in eutopic and ectopic endometrium of women with endometriosis suggests that endogenous GnRH II-mediated cytostatic regulation may be impaired in the development of endometriosis.
3) Cetrorelix directly inhibits the proliferation of rat mature granulosa cells through mechanisms involving multiple events in cell cycle progression, including G2 phase cell cycle arrest coupled with down-regulation of cyclin B1-cdc2 complex levels, presumably attributable to an up-regulation of p53 levels and apoptosis.
4) Fas/Fas ligand system is involved in inducing apoptosis through activation of a caspase-mediated cascade in rat granulosa cells, which is coupled with a decrease in iNOS expression. NO inhibits Fas/Fas ligand system-induced apoptosis by suppressing activation of the caspases, pointing to a cross-talk between Fas/Fas ligand system-induced apoptosis pathway and NO-mediated anti-apoptotic pathway in ovarian follicle atresia.
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