| Project/Area Number |
14571540
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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 | Gunma University |
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Principal Investigator |
SHINOZAKI Hiromitsu Gunma University, Medicine, Research Associate, 医学部, 助手 (30334139)
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| Co-Investigator(Kenkyū-buntansha) |
MINEGISHI Takashi Gunma University, Medicine, Professor, 医学部, 教授 (00209842)
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| Project Period (FY) |
2002 – 2003
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| Project Status |
Completed (Fiscal Year 2003)
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| Budget Amount *help |
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2003: ¥1,300,000 (Direct Cost: ¥1,300,000)
Fiscal Year 2002: ¥2,200,000 (Direct Cost: ¥2,200,000)
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| Keywords | LH receptor / gonadotropin receptor / GPCRs / constitutively active mutant / cAMP / phosphodiesterase / precocious puberty / ヒトLHレセプター / 点突然変異 / TGF-β |
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| Research Abstract |
The human LH receptor belongs to the family of G protein-coupled receptor. The LH receptor is expressed in the gonad, where it plays a pivotal role in both male and female reproductive physiology. On a cellular level, the binding of LH to the LH-R on gonadal target cells causes the stimulation of Gs, which in turn activates adenylyl cyclase, resulting in increased intracellular concentrations of cAMP.
In our recent experiment, the LH-R (L457R) mutant was both constitutively active and unresponsive to further hormonal stimulation as determined on both intact cells and isolated membranes. When coexpressed at submaximal concentrations, L457R does not decrease the cell surface expression of LH-R. Coexpression of L457R, however, causes an attenuation of LH-stimulated cAMP production by LH-R. We found that this attenuation was caused by an activation of the phosphodiesterase (PDE) 4D3.
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