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

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dc.contributor.authorLucas, Thais Fabiana Gameiro [UNIFESP]
dc.contributor.authorRoyer, Carine [UNIFESP]
dc.contributor.authorSiu, Erica Rosanna [UNIFESP]
dc.contributor.authorLazari, Maria de Fatima Magalhaes [UNIFESP]
dc.contributor.authorPorto, Catarina Segreti [UNIFESP]
dc.contributor.institutionUniversidade Federal de São Paulo (UNIFESP)
dc.date.accessioned2016-01-24T14:05:14Z
dc.date.available2016-01-24T14:05:14Z
dc.date.issued2010-08-01
dc.description.abstractThe 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.en
dc.description.affiliationUniversidade Federal de São Paulo, Sect Expt Endocrinol, Dept Pharmacol, Escola Paulista Med,INFAR, BR-04044020 São Paulo, Brazil
dc.description.affiliationUnifespUniversidade Federal de São Paulo, Sect Expt Endocrinol, Dept Pharmacol, Escola Paulista Med,INFAR, BR-04044020 São Paulo, Brazil
dc.description.sourceWeb of Science
dc.description.sponsorshipFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)pt
dc.description.sponsorshipConselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)pt
dc.description.sponsorshipIDFAPESP: 2004/01152-0pt
dc.description.sponsorshipIDFAPESP: 2007/52471-6pt
dc.format.extent307-317
dc.identifierhttps://dx.doi.org/10.1095/biolreprod.110.084160
dc.identifier.citationBiology of Reproduction. Madison: Soc Study Reproduction, v. 83, n. 2, p. 307-317, 2010.
dc.identifier.doi10.1095/biolreprod.110.084160
dc.identifier.issn0006-3363
dc.identifier.urihttps://repositorio.unifesp.br/handle/11600/32743
dc.identifier.wosWOS:000280149800018
dc.language.isoeng
dc.publisherSoc Study Reproduction
dc.relation.ispartofBiology of Reproduction
dc.rightsinfo:eu-repo/semantics/restrictedAccess
dc.subjectEstradiolen
dc.subjectEstradiol receptoren
dc.subjectGPERen
dc.subjectIntracellular signalingen
dc.subjectMechanisms of hormone actionen
dc.subjectSertoli cellsen
dc.subjectSignal transductionen
dc.titleExpression and Signaling of G Protein-Coupled Estrogen Receptor 1 (GPER) in Rat Sertoli Cellsen
dc.typeinfo:eu-repo/semantics/article
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