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

Rossella Cannarella,Cinzia Lilli,Iva Arato,Angela Alamo,Sandro La Vignera,Rosita A Condorelli,Riccardo Calafiore,Francesca Mancuso,Catia Bellucci,Federica Barbagallo,Aldo E Calogero,Giovanni Luca

doi:10.3390/jcm8050577

Rossella Cannarella, Cinzia Lilli + Show 10 more

Open Access

https://doi.org/10.3390/jcm8050577

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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.

Highlights

Follicle-stimulating hormone (FSH) is required for normal spermatogenesis [1]
A number of studies have assigned a role in Sertoli cells (SCs) function to the insulin-like growth factor 1 receptor (IGF1R), which belongs to the tyrosine kinases receptor family [3]
We evaluated the effects of FSH on MYPT1668, ERK 1/2, AKT308, AKT473, Jun N-terminal kinase (JNK) phosphorylation in purified and functional porcine neonatal SCs, with and without pre-treatment with the IGF1R inhibitor NVP-AEW541 and the phosphatase 1β (PP1β) inhibitor tautomycin

Summary

Introduction

Follicle-stimulating hormone (FSH) is required for normal spermatogenesis [1]. A deeper insight into the molecular mechanisms involved in FSH signaling in Sertoli cells (SCs) might help to elucidate some cases of unexplained male infertility. As for many G protein-coupled receptors (GPCRs), the FSH receptor (FSHR), once over stimulated by FSH, triggers Gαs, which activates the adenylate cyclase, resulting in increased intracellular cAMP levels. The latter leads to protein kinase A (PKA) activation, which in turn stimulates many different transcription factors [2]. The IGF1R is expressed in SCs and is required for testis development [4] and SC proliferation [5]

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