Concomitant Effects of Growth Hormone on Secretion of Insulin-Like Growth Factor I and Progesterone by Cultured Porcine Granulosa Cells*

Abstract

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.

Growth hormone co-treatment within a GnRH agonist long protocol in patients with poor ovarian response: a prospective, randomized, clinical trial

“…Growth hormone is reported to modulate the action of FSH on granulosa cells by up-regulating the local synthesis of insulin-like growth factor-I. The IGF-I amplifies the effect of gonadotropin action at the level of both the granulosa and theca cell [4,5]. Results from the published studies were conflicting regarding the effect of GH during controlled ovarian stimulation for IVF [6,7].…”

Growth hormone (GH) and reproduction: a review

“…Also the type 1 IGF receptor of Leydig cells was up regulated by GH (Lin et al 1988). Furthermore, GH injections to immature, hypophysectomized female rat increase the ovarian content of IGF-I (Davoren and Hsueh 1986), and porcine granulosa cell IGF-I production is GH stimulated in vitro (Hsu and Hammond 1987).…”

“…A small stimulation of progesterone by GH alone was first noted by Hsu and Hammond (1987). More recently Mason et al (1990) reported a potent stimulatory effect of hGH (10 ng/ml for 48h) on the production of E 2 by human granulosa cells, which was not dependant on FSH action.…”

“…This effect was mainly exerted by an amplification of gonadotropin actions (Jia et al 1986;Hsu and Hammond 1987;Hutchinson et al 1988). In some of these studies the GH effects were mimicked by IGF-I, involved enhanced LH receptor induction, or had a possible influence on cAMP synthesis.…”

“…Furthermore, IGF-I, IGF-Ireceptors and IGFBP appear to be strongly regulated by FSH (but also by LH and E 2 ) in granulosa cells (Hsu and Hammond 1987;Hernandez et al 1991), by FSH in Sertoli cells and by LH in Leydig cells (Avallet et al 1991), or by locally (intragonadal) produced factors. For these reasons, this growth factor is generally considered to amplify gonadotropin hormone action and/or to mediate the influence of FSH and LH on the gonads while potential GH effects are often minimized Hammond et al 1991).…”