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

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dc.contributor.author Royer, Carine [UNIFESP]
dc.contributor.author Lucas, Thais F. G. [UNIFESP]
dc.contributor.author Lazari, Maria F. M. [UNIFESP]
dc.contributor.author Porto, Catarina S. [UNIFESP]
dc.date.accessioned 2016-01-24T14:27:00Z
dc.date.available 2016-01-24T14:27:00Z
dc.date.issued 2012-04-01
dc.identifier http://dx.doi.org/10.1095/biolreprod.111.096891
dc.identifier.citation Biology of Reproduction. Madison: Soc Study Reproduction, v. 86, n. 4, 13 p., 2012.
dc.identifier.issn 0006-3363
dc.identifier.uri http://repositorio.unifesp.br/handle/11600/34726
dc.description.abstract The 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.sponsorship Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
dc.description.sponsorship Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)
dc.format.extent 13
dc.language.iso eng
dc.publisher Soc Study Reproduction
dc.relation.ispartof Biology of Reproduction
dc.rights Acesso aberto
dc.subject CREB en
dc.subject ESR1 en
dc.subject estradiol/estradiol receptor en
dc.subject GPER en
dc.subject gene regulation en
dc.subject Sertoli cells en
dc.subject signal transduction en
dc.title 17Beta-Estradiol Signaling and Regulation of Proliferation and Apoptosis of Rat Sertoli Cells en
dc.type Artigo
dc.contributor.institution Universidade Federal de São Paulo (UNIFESP)
dc.description.affiliation Universidade Federal de São Paulo, Dept Pharmacol, Sect Expt Endocrinol, Escola Paulista Med,INFAR, BR-04044020 São Paulo, Brazil
dc.description.affiliationUnifesp Universidade Federal de São Paulo, Dept Pharmacol, Sect Expt Endocrinol, Escola Paulista Med,INFAR, BR-04044020 São Paulo, Brazil
dc.description.sponsorshipID FAPESP: 2007/52471-6
dc.description.sponsorshipID FAPESP: 2010/52306-8
dc.identifier.doi 10.1095/biolreprod.111.096891
dc.description.source Web of Science
dc.identifier.wos WOS:000302767300011



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