Effects of GH and IGF1 on Basal and FSH-Modulated Porcine Sertoli Cells In-Vitro

Abstract

Several lines of evidence suggest that insulin-like growth factor 1 (IGF1) is involved in Sertoli cell (SC) proliferation and that its receptor (IGF1R) could mediate follicle-stimulating hormone (FSH) effects. To examine the role of the growth hormone (GH)-IGF1 axis on SC function, we evaluated the effects of GH and IGF1 on basal and FSH-modulated SC proliferation, as well as on anti-Müllerian hormone (AMH) and inhibin B expression and secretion in-vitro. SCs from neonatal pigs were incubated with (1) placebo, (2) 100 nM highly purified urofollitropin (hpFSH), (3) 100 nM recombinant GH (rGH), (4) 100 nM recombinant IGF1 (rIGF1), (5) 100 nM hpFSH plus 100 nM rGH, (6) 100 nM hpFSH plus 100 nM rIGF1, for 48 h. We found that IGF1, but not FSH nor GH, stimulated SC proliferation. Furthermore, an inhibitory effect of FSH, GH and IGF1 on AMH secretion, and a stimulatory role of FSH and IGF1, but not GH, on inhibin B secretion were found. These results suggest that the GH-IGF1 axis influences basal and FSH-modulated SC proliferation and function. We speculate that SC proliferation occurring in childhood might be supported by the increased serum IGF1 levels observed during this period of life.

Single-cell analysis of developing and azoospermia human testicles reveals central role of Sertoli cells

“…In infancy and early childhood, Sertoli cells of Stage_a are predominant and proliferate vigorously, with characteristics similar to those of stem cells. This may be due to various factors secreted by early Leydig cells, such as IGF 25 . Rapid amplification helps to increase the volume of seminiferous tubules.…”

Disorders of Puberty: Endocrinology of the Pre-Pubertal Testis

“…Cannarella et al report, for the first time, the role of the IGF1 receptor (IGF1R) in SCs, where they play a role similar to that already found in granulosa cells [1]. Other in vitro studies in this Special Issue [2,3] evaluate how incubation with follicle-stimulating hormone (FSH), GH, IGF1, or insulin impacts SC proliferation, AMH, and inhibin B secretion. Interestingly, these findings somehow question the role of FSH in SC proliferation in vitro, since no proliferative effect was found after 48 h of incubation.…”

Commentary: Molecular Mechanisms of Action of FSH

“…In these primary cultures, inhibition of the IGF1R affects the FSH capacity to phosphorylate target proteins (4). Similarly to FSH, IGF1 down-regulates antiMullerian hormone (AMH) gene expression and protein secretion, and enhances those of inhibin B (9). Co-incubation with both IGF1 and FSH results in a higher suppression of AMH secretion compared to that obtained with FSH alone (9).…”

“…Similarly to FSH, IGF1 down-regulates antiMullerian hormone (AMH) gene expression and protein secretion, and enhances those of inhibin B (9). Co-incubation with both IGF1 and FSH results in a higher suppression of AMH secretion compared to that obtained with FSH alone (9). This likely suggests an enhancing effect of IGF1 on FSH.…”

“…This likely suggests an enhancing effect of IGF1 on FSH. Furthermore, differently from FSH, IGF1 stimulates Sertoli cell proliferation, whereas FSH was able to stimulate cell proliferation only when co-administered with IGF1 (9).…”