2007 Fiscal Year Final Research Report Summary
Investigation for the mechanism of reproductive endocrine regulation by bone morphogenetic proteins
| Project/Area Number |
18591026
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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 |
Endocrinology
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| Research Institution | Okayama University |
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Principal Investigator |
OTSUKA Fumio Okayama University, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Assistant Professor (40362967)
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| Project Period (FY) |
2006 – 2007
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| Keywords | Endocrine / Granulosa cells / Bone morphogenetic proteins / Steroidogenesis / Estrogen / Growth factor / Gonadotropins / Infertility |
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| Research Abstract |
Normal follicular development is controlled by gonadotropins as well as ovarian growth factors, in which bone morphogenetic proteins (BMPs) regulate folliculogenesis and steroidogenesis. We studied the regulatory mechanism of BMPs on follicule-stimulating hormone (FSH)-induced steroidogenesis by rat primary granulosa cells with oocytes. Our studies in 2006 uncovered a new interaction between BMPs and MAP kinase (MAPK) signaling plays key physiological roles in differential regulation of steroidogenesis. BMP-7 preferentially increased FSH-induced estradiol production through inhibiting ERK phosphorylation in the presence of oocytes. In a research plan for 2007, we investigated roles of p38 MAPK pathway in regulating steroidogenesis. FSH and activin independently activated p38 MAPK phosphorylation in granulosa cells. Notably, BMP-2 and BMP-4 enhanced FSH-induced p38 phosphorylation in granulosa cells and the effect was further augmented by oocytes. Thus, BMP-2, -4, -6 and -7 differentially regulate FSH-induced steroidogenesis by stimulating FM-induced MAPK signaling. The oocyte-granulosa cell communication is crucial for differential regulation of FSH-induced steroidogenesis in normal follicular development. Given the fact that each BMP is involved in the key process of normal folliculogenesis, BMP would be a suitable marker for clinical diagnosis of follicular conditions as well as a candidate for therapeutic agents for ovarian dysfunction.
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