Expression and Signaling of G Protein-Coupled Estrogen Receptor 1 (GPER) in Rat Sertoli Cells

Autor(es)

Lucas, Thais F. G. ^[1] ; Royer, Carine ^[1] ; Siu, Erica R. ^[1] ; Lazari, Maria Fatima M. ^[1] ; Porto, Catarina S. ^[1]

Afiliação do(s) autor(es)

^[1] Univ Fed Sao Paulo, Sect Expt Endocrinol, Dept Pharmacol, Escola Paulista Med, INFAR, BR-04044020 Sao Paulo - Brazil

• Tipo de documento: Artigo Científico
• Fonte: BIOLOGY OF REPRODUCTION; v. 83, n. 2, p. 307-317, AUG 2010.
• Citações Web of Science: 58

Resumo

The aim of the present study was to investigate the expression and signaling of the G protein-coupled estrogen receptor 1 (GPER) in cultured immature rat Sertoli cells-in which we have previously described the classical estrogen receptors (ESR1 and ESR2). Expression of GPER in cultured Sertoli cells from 15-day-old rats was detected by RT-PCR and immunoassays. Gper transcripts also were present in testes from 5-, 15-, and 120-day-old rats. Short-term treatment of Sertoli cells with 17beta-estradiol (E2), the GPER agonist G-1, or the ESR antagonist ICI 182,780 (ICI) rapidly activated MAPK3/1 (ERK1/2), even after down-regulation of ESR1 and ESR2, suggesting a role for GPER in the rapid E2 action in these cells. MAPK3/1 phosphorylation induced by ICI or G-1 was blocked by pertussis toxin, selective inhibitor of the SRC family of protein tyrosine kinases, metalloprotease inhibitor, MAP2K1/2 inhibitor, and epidermal growth factor receptor (EGFR) kinase inhibitor. Furthermore, E2, but not G-1, induced up-regulation of cyclin D1 in the Sertoli cells. This effect was blocked by ICI. E2 and G-1 decreased BAX and increased BCL2 expression and these effects were blocked by MAP2K1/2 inhibitor and EGFR kinase inhibitor. The pretreatment with ICI did not block the effect of E2. Taken together, these results indicate that in Sertoli cells 1) GPER-mediated MAPK3/1 activation occurs via EGFR transactivation through G protein beta gamma subunits that promote SRC-mediated metalloprotease-dependent release of EGFR ligands, which bind to EGFR and lead to MAPK3/1 phosphorylation; 2) E2-ESRs play a role in Sertoli cell proliferation; and 3) E2-GPER may regulate gene expression involved with apoptosis. ESR and GPER may mediate actions important for Sertoli cell function and maintenance of normal testis development and homeostasis. (AU)

• Processo FAPESP: 07/52471-6 - Mecanismo de ação não-genômica do estrógeno em célula de Sertoli de ratos
• Beneficiário: Catarina Segreti Porto
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 04/01152-0 - Receptores muscarínicos em células de Sertoli de ratos: expressão e regulação dos receptores, sinalização intracelular e função
• Beneficiário: Catarina Segreti Porto
• Modalidade de apoio: Auxílio à Pesquisa - Regular