| Project/Area Number |
14571581
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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 | Kyorin University |
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Principal Investigator |
IWASHITA Mitsutoshi Kyorin University, Obstetrics & Gynecology, Professor, 医学部, 教授 (30124936)
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| Co-Investigator(Kenkyū-buntansha) |
ANDO Motomu Kyorin University, Obstetrics & Gynecology, Assistant Professor, 医学部, 講師 (10301483)
KATSUMATA Yuuko Kyorin University, Obstetrics & Gynecology, Assistant, 医学部, 助手 (00246357)
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| Project Period (FY) |
2002 – 2004
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| Project Status |
Completed (Fiscal Year 2004)
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| Budget Amount *help |
¥2,900,000 (Direct Cost: ¥2,900,000)
Fiscal Year 2004: ¥600,000 (Direct Cost: ¥600,000)
Fiscal Year 2003: ¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 2002: ¥1,200,000 (Direct Cost: ¥1,200,000)
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| Keywords | Insulin-like growth factor / IGF-binding protein / FSH / follicular growth / protease / granulose cell / estradiol / IGF-II / follicular develoment / IGFBP-4 / protease / follice development / 卵巣 / 卵胞 / IGF |
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| Research Abstract |
Follicular fluid from dominant follicles but not atretic follicles contains insulin-like growth factor (IGF) binding protein-4 (IGFBP-4) proteolytic activity. The effect of FSH and IGFs on IGFBP-4 proteolytic activity was studied using granulosa cell culture. Proteolytic activity was assessed by the incubation of [^<125>I]IGFBP-4 with medium and cleaved products were analyzed by autoradiography. The iodinated IGFBP-4 was cleaved into 18 kDa fragment when cells were incubated with FSH or IGFs while IGFBP-4 was remained intact in control culture. Inhibition of IGFBP-4 degradation by several protease inhibitors suggests that IGFBP-4 degradation was induced by a metalloserine protease. The degradation of IGFBP-4 was not stimulated when cells were incubated with the IGF-I analogue, LR3-IGF-I, and insulin that bind to IGF-I receptor but have less or no affinity for IGFBPs. Addition of IGFs but not FSH to medium from untreated GC culture stimulated proteolysis of [^<125>I]IGFBP-4. Similarly, exogenously added covalently cross-linked [^<125>I]IGF-II-IGFBP-4 complexes were proteolyzed, however, IGFs did not enhance the degradation of the complexes. These results suggest that human granulosa cells produce IGFBP-4 protease and that the increased susceptibility of IGFBP-4 to proteolysis is induced by the binding of IGFs to IGFBP-4. These novel mechanisms may be important to modulate IGF-mediated folliculogenesis in the ovary.
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