| Project/Area Number |
07671827
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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 | Tokyo Women's Medical College |
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Principal Investigator |
ADACHI Tomoko Tokyo Women's Medical College, School of Medicine, Department of Obstetrics and Gynecology, Associate Professor, 医学部, 助教授 (70175173)
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| Co-Investigator(Kenkyū-buntansha) |
HARA Makoto Tokyo Women's Medical College, School of Medicine, Department of Obstetrics and, 医学部, 助手 (70246601)
IWASHITA Mitsutoshi Tokyo Women's Medical College, School of Medicine, Maternal and Perinatal Center, 医学部, 教授 (30124936)
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| Project Period (FY) |
1995 – 1996
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| Project Status |
Completed (Fiscal Year 1996)
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| Budget Amount *help |
¥2,000,000 (Direct Cost: ¥2,000,000)
Fiscal Year 1996: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 1995: ¥1,000,000 (Direct Cost: ¥1,000,000)
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| Keywords | Growing follicle / Atretic follicle / Granulosa cells / Estradiol secretion / IGF-I / IGF binding proteins / Proteolytic enzyme / FSH / 卵巣顆粒膜細胞 / IGF |
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| Research Abstract |
1) Role of IGF-I and IGF binding proteins in estradiol secretion by human luteinizing graunlosa cells.
IGF-I stimulated the secretion of E2 in a dose dependent fashion by human luteinizing granulosa cells which were collected from the patients under IVF-ET program. While IGFBP-1 and -3 did not influence the basal secretion of E2, the same amount of IGFBP_s reduced the secretion of E2 stimulated by IGF-I.Both IGFBP-1 and -3 inhibited ^<125>I-IGF-I binding to membrane receptors. These data suggested that IGFBP_s might be aregulator of IGF-I actionin the ovary and inhibitory effects of IGFBP_s on IGF-I-stimulated E2 release were achieved by inhibiting IGF-I binding to its receptors.
2) IGF-I system-mediated FSH action on human granulosa cells
Addition of IGF-I with FSH highly stimulated the secretion of E2 by human luteinizing granulosa cells. To evaluate the regulation of the secretion of IGFBP_s by FSH in human granulosacells, granulosacells were in cubated with or without FSH.FSH in hibit
… More
ed the secretion of IGFBP-1 dose dependently. FSH did not in hibit the secretion of immunore active IGFBP-3, but inhibited the binding activity of IGFBP-3 evaluated by Westem ligandblot. To assess the protease activity, ^<125>I-IGFBP-3 was in cubated with the cultured medium. ^<125>I-IGFBP-3 degraded into small fragments when it was in cubated with the cultured medium treated with FSH.These data suggested that FSH enhances the action of IGF-I in human granulosa cells by in hibiting the secretion of IGFBP-1 and the binding activity of IGFBP-3 by stimulating the proteolysis of IGFBP-3.
3) Physiological significance of IGF-I and IGFBP_s in follicular development and atresia.
To evaluate the change of intrafollicular environment according to follicle growth of atresia, levels of steroid hormones and IGF-I and IGFBP_s in the follicular fluid of various follicles, which were collected from patients under laparotomies, were measured. The ratio of androstenedione (A) to E2 was more than 10.0 in atretic follicles and less than 0.1 in mature follicles. In atretic follicles levels of IGF-I were significantly lower (P<0.05), moreober, binding activities of IGFBP-2 and -4 were higher, compared to those in mature follicles whose IGFBP-4 proteolysis was accerelated. Taken together, formation of the intrafollicular environment as high A and low E2 of atretic follicles might have relationship with the system of suppressing the biological activities of IGF-I via stimulating the binding activities of IGFBP-2 and -4. Less
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