The IGF1 Receptor Is Involved in Follicle-Stimulating Hormone Signaling in Porcine Neonatal Sertoli Cells

Abstract

Experimental evidence has shown that the IGF1 receptor (IGF1R) is involved in testicular development during embryogenesis. More recently, data gathered from mice granulosa cells and zebrafish spermatogonia suggest that IGF1R has a role in Follicle-stimulating hormone (FSH) signaling. No evidence has been reported on this matter in Sertoli cells (SCs) so far. The aim of the study was to evaluate the role, if any, of the IGF1R in FSH signaling in SCs. The effects of FSH exposure on myosin-phosphatase 1 (MYPT1), ERK 1/2, AKT308, AKT473, c-Jun N-terminal kinase (JNK) phosphorylation and on anti-Müllerian hormone (AMH), inhibin B and FSH receptor (FSHR) mRNA levels were assessed with and without the IGF1R inhibitor NVP-AEW541 in purified and functional porcine neonatal SCs. Pre-treatment with NVP-AEW541 inhibited the FSH-induced MYPT1 and ERK 1/2 phosphorylation, decreased the FSH-dependent Protein kinase B (AKT)308 phosphorylation, but did not affect the FSH-induced AKT473 and JNK phosphorylation rate. It also interfered with the FSH-induced AMH and FSHR down-regulation. No influence was observed on the FSH-stimulated Inhibin B gene expression. Conclusion. These findings support the role of theIGF1R in FSH signaling in porcine SCs. The possible influence of IGF1 stimulation on the FSH-mediated effects on SCs should be further explored.

Commentary: Molecular Mechanisms of Action of FSH

“…Particularly, insulin-like growth factor 1 (IGF1) and its receptor (IGF1R) have already been showed to act in FSH signaling in granulosa cells (2, 3). Similarly, we recently confirmed such evidence in porcine Sertoli cells (4).…”

Effects of Insulin on Porcine Neonatal Sertoli Cell Responsiveness to FSH In Vitro

“…FSH has recently been shown to enhance myosin-phosphatase 1 (MYPT1), ERK 1/2, AKT 308 , AKT 473 and to decrease JNK phosphorylation rates. These effects were partially or totally hindered by pre-treatment with the insulin-like growth factor 1 receptor (IGF1R) inhibitor NVP-AEW541, thus suggesting a role for IGF1R in FSH signaling [7]. Studies carried out in granulosa cells supported these data [26] and further indicated that insulin-receptor substrate 1 (IRS1) might be the hub linking FSHR, belonging to the G protein-coupled receptors (GPCRs), and IGF1R, which is a tyrosine kinase receptor [27].…”

“…Once stimulated by FSH, as for many GPCRs, the FSHR triggers the Gαs, which activates the adenylate cyclase, resulting in increased intracellular cAMP levels. The latter leads to protein kinase A (PKA) activation [5], which in turn triggers the following major signaling pathways: the phosphoinositide 3-kinase (PI3K)/AKT pathway and the mitogen-activated protein kinase (MAPK) pathway [6,7]. The first is committed to preventing apoptosis, cell proliferation and glucose transport.…”

“…The first is committed to preventing apoptosis, cell proliferation and glucose transport. It is activated in an insulin-like growth factor 1 receptor (IGF1R)-dependent manner [7]. The MAPK pathways, including ERK1/2 and JNK, regulate cell proliferation, differentiation and apoptosis [6].…”

Disorders of Puberty: Endocrinology of the Pre-Pubertal Testis

“…Pre-pubertal porcine SCs represent the in vitro system most similar to children's SCs. 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.…”