Growth hormone (GH) deficiency in rats is associated with decreased ovarian steroidal responsiveness to gonadotropins, possibly through a reduction in the production of the GH-dependent Somatomedin C/insulinlike growth factor I (SM C/IGF I). We have investigated the direct effects of synthetic SM C/IGF I on gonadotropin-stimulated ovarian steroidogenesis in vitro. Granulosa cells were cultured in a serum-free medium for 48 h in the presence of follicle-stimulating hormone (FSH), with or without SM C/IGF I. FSH dose-dependently increased both estrogen and progestin production. Concomitant treatment with SM C/IGF I led to a dose-dependent augmentation of progestin secretion over the full range of FSH doses tested, by a maximum of 2.3- to 2.6-fold. FSH-stimulated estrogen was enhanced by up to 2.4-fold but only at low doses of FSH. SM C/IGF I-enhanced progestin production was associated with increased pregnenolone production and 3 beta-hydroxysteroid dehydrogenase activity, whereas augmented estrogen production appeared to be due to enhanced aromatase activity. The actions of SM C/IGF I, at physiologically relevant concentrations were correlated with increased extracellular cAMP accumulation and cellular protein content but were independent of any change in cell number or viability. In contrast to SM C/IGF I, the closely related peptide multiplication-stimulating activity decreased estrogen production while increasing progestin metabolite accumulation. The present results indicate that the GH-dependent peptide SM C/IGF I may play a role in ovarian development by enhancing gonadotropin-stimulated granulosa cell steroidogenesis.

The effect of insulin-like growth factor-I (IGF-I), epidermal growth factor (EGF), fibroblast growth factor (FGF) and nerve growth factor (NGF) on production of oxytocin and progesterone by cultured bovine granulosa and luteal cells was studied. Secretion of oxytocin was stimulated, in a dose-dependent manner, by IGF-I at 48 and 120 h of culture to levels much higher than those after stimulation with LH, FSH, EGF, FGF or NGF. A similar effect of IGF-I was observed for progesterone but, in contrast to oxytocin, secretion of progesterone was not increased by EGF, NGF or FGF. During primary culture, for 4 h, of dispersed bovine luteal cells obtained from corpora lutea between days 4 and 10 of the oestrous cycle, all the growth factors tested failed to stimulate secretion of oxytocin or progesterone. The data suggest the relevance of growth factors (especially IGF-I) for ovarian physiology and their possible importance for differentiation of follicles and luteinization.