Regulation and physiological role of insulin-like-growth-factor-binding protein-1 in human granulosa cells

The present study was undertaken to elucidate the physiological role and the regulation of insulin-like growth factor (IGF)-binding protein-1 (IGFBP-1) in human luteinizing granulosa cells. IGFBP-1 abolished IGF-I-stimulated estradiol production by luteinizing granulosa cells in a dose-dependent manner with a 50% inhibitory concentration (IC50) of 0.27 nM. Similarly, IGFBP-1 inhibited 125I-IGF-I binding to granulosa cells. IGFBP-1 was identified by Western immunoblot and specific enzyme immunoassay in the granulosa-cell-conditioned medium after 24 h culture. Immunoreactive IGFBP-1 released into the medium was inhibited by both IGF-I and follicle-stimulating hormone dose-dependently with an IC50 of 0.14 and 0.13 nM, respectively, while human chorionic gonadotropin-stimulated IGFBP-1 release with a 50% effective dose (ED50) of 0.6 nM. These results suggest that IGFBP-1 is involved in follicular development and granulosa cell differentiation in the human ovary and that gonadotropins may influence IGF-I action by modifying IGFBP-1 levels within the ovary.