| Project/Area Number |
18591822
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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 | Yamagata University |
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Principal Investigator |
TAKAHASHI Kazuhiro Yamagata University, Faculty of Medicine, Associate professor (20292427)
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| Co-Investigator(Kenkyū-buntansha) |
KURACHI Hirohisa Yamagata University, Faculty of Medicine, professor (40153366)
TSUTSUMI Seiji Yamagata University, Faculty of Medicine, Associate professor (50323168)
ABE Akiko Yamagata University, Faculty of Medicine, Associate professor (30359567)
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| Project Period (FY) |
2006 – 2007
|
| Project Status |
Completed (Fiscal Year 2007)
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| Budget Amount *help |
¥4,010,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥510,000)
Fiscal Year 2007: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
Fiscal Year 2006: ¥1,800,000 (Direct Cost: ¥1,800,000)
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| Keywords | estroeen / progesterone / neurite outgrowth / Rho / Akt |
|---|
| Research Abstract |
Estrogen (E2) has direct in vivo and in vitro effects, such as inducing neurite outgrowth, on neurons. We investigated the morphological changes and intracellular signaling pathway induced by E2 in neuroblastoma (SH-SY5Y) cells. The effect of medroxyprogesterone acetate (MPA) or progesterone (P4) on the E2-induced neurite outgrowth was also examined using SH-SY5Y cells. Neurite outgrowth was induced by E2 in association with the phosphorylation of both Akt and extracellular signal-regulated kinase (ERK). These effects of E2, except for ERK phosphorylation, were abolished by MPA but not by P4. Progesterone receptor antagonist RU486 blocked the inhibitory effects of MPA. Estrogen receptor antagonist ICI 182, 780 and phosphatidylinositol 3-kinase inhibitor LY294002 inhibited the E2-induced neurite outgrowth. Because the Rho family of small GTPases has been shown to be involved in the regulation of neurite outgrowth, we examined the cross-talk among Rac1, Cdc42 and RhoA in the E2-induced neurite outgrowth. E2 immediately increased the Rac1 and Cdc42 activity and decreased the RhoA activity. E2-induced neurite outgrowth was attenuated in cells expressing dominant-negative mutants for Rac1 or Cdc42. These results suggest that regulation of Rho family GTPase activity by E2 is important for the neurite outgrowth in neuroblastoma cells, and that MPA, but not P4, may have an antagonistic effect against E2.
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