17Beta-Estradiol Signaling and Regulation of Proliferation and Apoptosis of Rat Sertoli Cells

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dc.contributor.authorRoyer, Carine [UNIFESP]
dc.contributor.authorLucas, Thais Fabiana Gameiro [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.accessioned2016-01-24T14:27:00Z
dc.date.available2016-01-24T14:27:00Z
dc.date.issued2012-04-01
dc.description.abstractThe aim of the present study was to investigate the intracellular signaling events downstream of the classical estrogen receptors (ESRs) and G protein-coupled estrogen receptor 1 (GPER) involved in regulation of proliferation and apoptosis of rat Sertoli cells, in which we have previously described ESR1, ESR2, and GPER. ESRs play a role in Sertoli cell proliferation, and GPER, but not ESRs, plays a role modulating gene expression involved with apoptosis. the present study shows that 17beta-estradiol (E2) and the GPER-selective agonist G-1 rapidly activate phosphatidylinositol 3-kinase (PIK3)/serine threonine protein kinase (AKT) and cyclic AMP response element-binding (CREB) phosphorylation. E2 and the ESR1-selective agonist 4,4',4 ''-(4-propyl-(1H)-pyrazole-1,3,5-triyl)trisphenol (PPT) increase the expression of cyclin D1 (CCND1), whereas the ESR2-selective agonist 2,3-bis(4-hydroxyphenyl)-propionitrile (DPN) and G-1 do not change the expression of this protein, suggesting that ESR1 is the upstream receptor regulating Sertoli cell proliferation. E2- or PPT-ESR1, through activation of epidermal growth factor receptor (EGFR)/mitogen-activated protein kinase 3/1 (MAPK3/1) and PIK3 pathways, induces upregulation of CCND1. KG-501, the compound that disrupts the phospho-CREB/CREB binding protein (CBP) complex, does not change E2-or PPT-ESR1-mediated CCND1 expression, suggesting that phospho-CREB/cyclic AMP response element/CBP is not involved in the expression of this protein. E2- or G-1-GPER, through activation of EGFR/MAPK3/1 and PIK3 pathways, may be involved in the upregulation of antiapoptotic proteins BCL2 and BCL2L2. E2- or G-1-GPER/EGFR/MAPK3/1/phospho-CREB decreases BAX expression. Taken together, these results show a differential effect of E2-GPER on the CREB-mediated transcription of proapoptotic and antiapoptotic genes of the same BCL2 gene family. ESR1 and GPER can mediate the rapid E2 actions in the Sertoli cells, which in turn can modulate nuclear transcriptional events important for Sertoli cell function and maintenance of normal testis development and homeostasis. Our findings are important to clarify the role of estrogen in a critical period of testicular development, and to direct further studies, which may contribute to better understanding of the causes of male infertility.en
dc.description.affiliationUniversidade Federal de São Paulo, Dept Pharmacol, Sect Expt Endocrinol, Escola Paulista Med,INFAR, BR-04044020 São Paulo, Brazil
dc.description.affiliationUnifespUniversidade Federal de São Paulo, Dept Pharmacol, Sect Expt Endocrinol, 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: 2007/52471-6pt
dc.description.sponsorshipIDFAPESP: 2010/52306-8pt
dc.format.extent13
dc.identifierhttps://dx.doi.org/10.1095/biolreprod.111.096891
dc.identifier.citationBiology of Reproduction. Madison: Soc Study Reproduction, v. 86, n. 4, 13 p., 2012.
dc.identifier.doi10.1095/biolreprod.111.096891
dc.identifier.issn0006-3363
dc.identifier.urihttps://repositorio.unifesp.br/handle/11600/34726
dc.identifier.wosWOS:000302767300011
dc.language.isoeng
dc.publisherSoc Study Reproduction
dc.relation.ispartofBiology of Reproduction
dc.rightsinfo:eu-repo/semantics/openAccess
dc.subjectCREBen
dc.subjectESR1en
dc.subjectestradiol/estradiol receptoren
dc.subjectGPERen
dc.subjectGene regulationen
dc.subjectSertoli cellsen
dc.subjectSignal transductionen
dc.title17Beta-Estradiol Signaling and Regulation of Proliferation and Apoptosis of Rat Sertoli Cellsen
dc.typeinfo:eu-repo/semantics/article
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