Comparison of growth hormone and insulin-like growth factor-I regulation of estradiol and progesterone production in human luteinized granulosa cells

Growth hormone (GH) appears to affect the timing of puberty in children. The effects of GH on puberty may be related to direct GH action on ovarian function or may be mediated by IGF-I. To determine the likelihood that GH has direct effects on ovarian function, we compared the ability of GH and IGF-I to increase luteinized granulosa cell steroidogenesis in the absence and presence of gonadotropins. Cells were obtained from women undergoing in vitro fertilization for tubal disorders or male factor infertility and were placed in static culture. GH alone failed to alter progesterone or estradiol accumulation in the medium of cultured luteinized granulosa cells. IGF-I produced no increase in progesterone accumulation but increased estradiol accumulation 5.6-fold compared with cells treated with vehicle. The combination of GH and FSH produced an 0.83-fold increase in estradiol accumulation, whereas the combination of IGF-I and FSH resulted in a 2.9-fold increase in estradiol accumulation above FSH alone. Thus the direct effects of GH on granulosa cell steroid synthesis are modest compared with those of IGF-I. If GH has an effect on ovarian development at puberty, it is likely to be mediated by a GH-induced increase in circulating IGF-I.