| Project/Area Number |
17590209
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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 |
Environmental physiology (including Physical medicine and Nutritional physiology)
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| Research Institution | Yokohama City University |
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Principal Investigator |
FUNABASHI Toshiya Yokohama City University, Graduate School of Medicine Department of Physiology, Associate Professor (70229102)
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| Co-Investigator(Kenkyū-buntansha) |
MITSUSHIMA Dai Yokohama City University Graduate School of Medicine, Graduate School of Medicine Department of Physiology, Associate Professor (70264603)
TAKASE Kenkichi Yokohama City University Graduate School of Medicine, Graduate School of Medicine Department of Physiology, Assistant Professor (80381474)
SAKAKIBARA Hideya Yokohama City University Graduate School of Medicine, Graduate School of Medicine Department of Obsterics and Gynecology, Associate Professor (60235140)
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| Project Period (FY) |
2005 – 2007
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| Project Status |
Completed (Fiscal Year 2007)
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| Budget Amount *help |
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2006: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 2005: ¥2,800,000 (Direct Cost: ¥2,800,000)
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| Keywords | gonadotropin / zonadotrovin-releasing hormone / estrogen / preoptic area / virus / surge / ovulation / puberty / 鋤鼻器 / サージ発生器 / 脳・神経 / pCREB |
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| Research Abstract |
The present study investigated the utility of model for in vitro GnRH surge generator by culturing the olfactory placode. We found that model was useful since blockade of cAMP production markedly attunated release of GnRH as did in vivo. In GT1-1 cells, the electrical activity examined by extracellular recording was sometimes related to Ca2+ oscillations. This result suggests that GTI-1 cells are useful as in vitro model for pulse generator. Next, we examined the possible role for glutamatergic neurons generating the surge of GnRH secretion. GluR1-C-tail, a dominant negative mutant of GluR1 (subunit of AMPA receptors), has been shown to act by competing with GluR1 for synaptic delivery during neural plasticity. GluR1-C-tail was expressed in the POA of female rats using lentivirus. Injection with GluR1-C-tail in adult rats had no effect on the surge of LH secretion. When the injection was done at 21-day, the onset of puberty was significantly delayed, by checking viginal opening. After that, the estrous cyclicity was checked by viginal smear and found that the rat injected with GIuR1-C-tail exhibited an irregular estrous cycle. The surge of luteinizing hormone (LH) secretion in the adult rat injected with GluR1-C-tail at 21-day was significantly attenuated, compared to the control rat. The result suggests that GluR1 -mediated plasticity occurs at the time of puberty and is important to maintain surge of LH secretion in adults. We are now examining the trafficking of GluR1 in GnRH neurons by a whole-cell voltage clamp recording. With regard to the role of CREB in the surge generator, we are currently examining the effects of mCREB (dominant negative) or cCREB (constitutively active) on the surge of LH secretion.
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