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

Autor(es)

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

• Tipo de documento: Artigo Científico
• Fonte: Reproduction; v. 152, n. 6, p. 613-628, DEC 2016.
• Citações Web of Science: 5

Resumo

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)

• Processo FAPESP: 10/10274-2 - Avaliação do papel da relaxina sobre passos iniciais e tardios da espermatogênese, em modelo de co-cultura de células germinativas e de Sertoli
• Beneficiário: Maria de Fátima Magalhães Lazari
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 14/05028-3 - Sinalização de relaxina em testículo: investigação da presença de isoformas de receptor RXFP1, da sinalização NOS/NO e da possível participação do receptor de glicocorticoide
• Beneficiário: Carla Macheroni Lima
• Modalidade de apoio: Bolsas no Brasil - Iniciação Científica
• Processo FAPESP: 14/08563-7 - Explorando a contribuição de novos receptores e vias de sinalização para o efeito modulador de relaxina sobre a proliferação e diferenciação de células de Sertoli
• Beneficiário: Maria de Fátima Magalhães Lazari
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 11/14262-1 - Papel da relaxina em diferentes fases do desenvolvimento de células de Sertoli: caracterização da sinalização intracelular, efeitos sobre a expressão gênica e proteica e modulação por FSH
• Beneficiário: Aline Rosa do Nascimento
• Modalidade de apoio: Bolsas no Brasil - Doutorado