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 a nd the regulation of insulin-like growth factor (IGF)-binding protein- 1 (IGFBP-1) in human luteinizing granulosa cells. IGFBP-1 abolished IG F-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 I-125-IGF-I binding to granulosa cells. IGFBP-1 was identified by Western immunoblot and specific enzy me immunoassay in the granulosa-cell-conditioned medium after 24 h cul ture. 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 gonadotr opin-stimulated IGFBP-1 release with a 50% effective dose (ED(50)) of 0.6 nM. These results suggest that IGFBP-1 is involved in follicular d evelopment and granulosa cell differentiation in the human ovary and t hat gonadotropins may influence IGF-I action by modifying IGFBP-1 leve ls within the ovary.