Crosstalk between FSH and relaxin at the end of the proliferative stage of rat Sertoli cells

Author(s)

Nascimento, Aline R. ; Macheroni, Carla ; Lucas, Thais F. G. ; Porto, Catarina S. ; Lazari, Maria F. M.

• Document type: Journal article
• Source: Reproduction; v. 152, n. 6, p. 613-628, DEC 2016.
• Web of Science Citations: 5

Abstract

Follicle-stimulating hormone (FSH) stimulates the proliferation of immature Sertoli cells through the activation of PI3K/AKT/mTORC1 and MEK/ERK1/2 pathways. Mature Sertoli cells stop proliferating and respond to FSH by stimulating cAMP production. To gain insight into possible mechanisms involved in this switch as well as the impact of paracrine factors that stimulate cell proliferation, we analyzed the effects of FSH and relaxin on intracellular signaling pathways involved with proliferation and differentiation in Sertoli cells from 15-day-old rats, which are close to the transition between the two stages. FSH stimulated H-3-thymidine incorporation and cyclin D1 expression, changes associated with proliferation. In contrast, FSH inhibited AKT and ERK1/2 phosphorylation, activated cAMP production and induced changes in several cell cycle genes that were compatible with differentiation. Relaxin also stimulated 3H-thymidine incorporation but increased phosphorylation of ERK1/2 and AKT. When both hormones were added simultaneously, relaxin attenuated FSH-mediated inhibition of ERK1/2 and AKT phosphorylation and FSH-mediated activation of cAMP production. FSH but not relaxin increased CREB phosphorylation, and relaxin but not FSH shifted NF-kappa B expression from the cytoplasm to the nucleus. Relaxin did not inhibit the effects of FSH on inhibin alpha and Bcl2 expression. We propose that at this time of Sertoli cell development, FSH starts to direct cells to differentiation through activation of cAMP/CREB and inhibition of ERK1/2 and AKT pathways. Relaxin counteracts FSH signaling through the inhibition of cAMP and activation of ERK1/2, AKT and NF-kappa B, but does not block the differentiation process triggered by FSH. (AU)

• FAPESP's process: 10/10274-2 - Analysis of the role of relaxin in early and late stages of spermatogenesis, using co-cultures of Sertoli and germ cells
• Grantee: Maria de Fátima Magalhães Lazari
• Support Opportunities: Regular Research Grants
• FAPESP's process: 14/05028-3 - Relaxin signaling in testis: investigation of the presence of isoforms of the RXFP1 receptor, NOS/NO signaling, and the possible participation of the glucocorticoid receptor
• Grantee: Carla Macheroni Lima
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• FAPESP's process: 14/08563-7 - Exploring possible new receptors and signaling pathways that may contribute to the modulatory effect of relaxin on proliferation and differentiation of Sertoli cells
• Grantee: Maria de Fátima Magalhães Lazari
• Support Opportunities: Regular Research Grants
• FAPESP's process: 11/14262-1 - Role of relaxin in different stages of Sertoli cell development: characterization of the intracellular signaling, effects on gene and protein expression and modulation by FSH
• Grantee: Aline Rosa do Nascimento
• Support Opportunities: Scholarships in Brazil - Doctorate