Role of IGF-I and IGF Binding Proteins in Regulation of Human Ovarian Function

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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 cellsAddition 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