Insulin-like growth factor-I (IGF-I) inhibits production of IGF-binding protein-1 while stimulating estradiol secretion in granulosa cells from normal and polycystic human ovaries.

We have investigated the actions of FSH and insulin-like growth factor-I (IGF-I) on the production of IGF-binding protein-1 (IGFBP-1) by granulosa cells from unstimulated normal and polycystic (PCO) human ovaries and related these effects to those on estradiol (E2). IGFBP-1 concentrations were measured in granulosa cell-conditioned medium (48-h culture with 10(-7) M testosterone) and follicular fluid. IGF-I (50 ng/mL), in the absence of FSH, stimulated E2 production by granulosa cells from both normal and polycystic ovaries, and there was a synergistic action between IGF-I and FSH. Granulosa cells secreted IGFBP-1 in concentrations ranging from 20-500 pg/1000 cells.48 h, with cells from two of four normal and three of four polycystic ovaries showing a dose-related increase in IGFBP-1 production in response to FSH. In contrast, the addition of as little as 100 pg/mL IGF-I to cells incubated with testosterone or testosterone plus FSH, caused complete inhibition of IGFBP-1 production. FSH treatment produced the expected dose-related increase in E2 accumulation. IGFBP-1 was detectable in fluid from all sizes of follicle tested, but there was no correlation of IGFBP-1 concentrations with follicle size and no difference between normal and polycystic ovaries. These data indicate that IGFBP-1 and E2 are differentially regulated by IGF-1 in the human ovary.