Direct Gonadotrophic Effect of Growth Hormone on Oestradiol Production by Human Granulosa Cells in Vitro

Abstract

In-vitro studies in both rodents and man suggest that GH can stimulate ovarian steroidogenesis, but it is not clear whether this effect is mediated by changes in circulating concentrations of insulin-like growth factor-1 (IGF-1) or whether it is a direct action on the ovary (or, indeed, both). In this study the effects of biosynthetic human GH (hGH) on the production of oestradiol and IGF-1 by human granulosa cells in culture were examined using ovarian tissue (from both normal and polycystic ovaries) which had not previously been exposed to exogenous gonadotrophin therapy. Addition of hGH (1 or 10 ng/ml) to the incubation medium resulted in a significant (1.7 to 3.6 fold) increase in oestradiol accumulation after 48h in culture. Human GH also had a significant additive effect on the dose-related responsiveness of granulosa cell oestradiol production to hFSH. Concentrations of IGF-1 in the medium were undetectable in each of these experiments. These studies demonstrate that hGH has a potent, direct stimulatory effect on production of oestradiol by the human ovary which is independent of the effect of FSH. These findings have important implications for understanding the physiological role of hGH in human ovarian function as well as for therapeutic use of biosynthetic hGH for induction of ovulation.

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

“…As higher concentrations of estradiol in pre-ovulatory follicular fluid predict a higher chance of pregnancy [13], GH administration early in the recruitment phase appears to be a better method to be employed in poor responders. Additional stimulating effect of GH on the production of estradiol by granulosa cells has previously been shown [14,15]. Further appropriately designed studies are needed to determine whether effects of GH on follicular fluid estradiol concentration are the only mechanism involved in the improvement of oocyte number and better clinical pregnancy rates in poor responder women or whether other mechanisms also play a role.…”

Ovarian Follicular Concentrations of Activin, Follistatin, Inhibin, Insulin-Like Growth Factor I (IGF-I), IGF-II, IGF-Binding Protein-2 (IGFBP-2), IGFBP-3, and Vascular Endothelial Growth Factor in Spontaneous Menstrual Cycles of Normal Women of Advanced Reproductive Age

“…IGF-I has been shown to serve as an intraovarian regulator of follicle function in rodents, and it exerts direct effects on human and rodent granulosa cell function (31,32). In vitro, IGF-I, in conjunction with gonadotropins, appears to have a role as a promoter of follicle growth (33) and steroid secretion (34,35) and as an antiatretic hormone (36).…”

Efficacy of growth hormone in improving the pregnancy rate in poor responders in ART

“…7 Growth hormone has shown to increase intra uterine IGF-1 levels. 8 The addition of IGF-1 to gonadotrophins in vitro culture of granulose cells have shown increased gonadotrophin action by several mechanisms like augmentation of aromatase activity, progesterone production, 17 betaestradiol production and luteinizing hormone receptor formation. 9 Several other studies have shown the beneficial effect of growth hormone on poor responders.…”