Concomitant effects of growth hormone on secretion of insulin-like growth factor I and progesterone by cultured porcine granulosa cells.

The observation that GH deficiency delays the onset of puberty has raised the question of the effect of GH on gonadal development. In addition, recent studies in the rat have indicated that GH is able to elevate ovarian levels of immunoreactive insulin-like growth factor I (iIGF-I) in vivo and enhance FSH-induced granulosa cell differentiation in vitro. To evaluate further the possibility of direct effects of GH on ovarian function, we have studied the action of GH on the secretion of iIGF-I and progesterone by cultured porcine granulosa cells from immature follicles. The effects of GH were compared with those of estradiol (E2) and FSH, hormones previously shown to stimulate steroidogenesis and iIGF-I production in this system. GH-stimulated cultures secreted 7.8 times as much iIGF-I per cell as control cultures, while cultures treated with E2 plus FSH secreted 4.5 times as much, and the combination of all three hormones produced an additional increment. The GH-dependent immunoreactivity was localized to two peaks on gel filtration which coeluted with authentic IGF-I and with an IGF-binding protein. In contrast to the results with iIGF-I secretion, GH was a relatively ineffective stimulator of progesterone secretion, resulting in levels 2.6 times the control value, compared to levels 7.4-fold the control value in cultures treated with E2 plus FSH. However, when the three agonists were combined, a synergistic interaction was observed which resulted in progesterone values 33.3 times the control value. In parallel studies, PRL was unable to mimic the effects of GH on iIGF-I or progesterone secretion. In summary, GH has direct stimulatory actions on porcine granulosa cells. Compared to E2 and FSH, established stimulators of these cells, GH is at least comparable in effectiveness with regard to iIGF-I secretion, but less effective as a stimulator of steroidogenesis. However, GH dramatically enhances the effects of E2 and FSH on progesterone secretion. These effects of GH could be important during the onset of puberty, when GH levels in plasma are elevated.