17Beta-Estradiol Signaling and Regulation of Proliferation and Apoptosis of Rat Sertoli Cells
Autor(a) principal: | |
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Data de Publicação: | 2012 |
Outros Autores: | , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Institucional da UNIFESP |
Texto Completo: | https://repositorio.unifesp.br/handle/11600/34726 https://dx.doi.org/10.1095/biolreprod.111.096891 |
Resumo: | 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. |
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Royer, Carine [UNIFESP]Lucas, Thais Fabiana Gameiro [UNIFESP]Lazari, Maria de Fatima Magalhaes [UNIFESP]Porto, Catarina Segreti [UNIFESP]Universidade Federal de São Paulo (UNIFESP)2016-01-24T14:27:00Z2016-01-24T14:27:00Z2012-04-01Biology of Reproduction. Madison: Soc Study Reproduction, v. 86, n. 4, 13 p., 2012.0006-3363https://repositorio.unifesp.br/handle/11600/34726https://dx.doi.org/10.1095/biolreprod.111.09689110.1095/biolreprod.111.096891WOS:000302767300011The 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.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Universidade Federal de São Paulo, Dept Pharmacol, Sect Expt Endocrinol, Escola Paulista Med,INFAR, BR-04044020 São Paulo, BrazilUniversidade Federal de São Paulo, Dept Pharmacol, Sect Expt Endocrinol, Escola Paulista Med,INFAR, BR-04044020 São Paulo, BrazilFAPESP: 2007/52471-6FAPESP: 2010/52306-8Web of Science13engSoc Study ReproductionBiology of ReproductionCREBESR1estradiol/estradiol receptorGPERGene regulationSertoli cellsSignal transduction17Beta-Estradiol Signaling and Regulation of Proliferation and Apoptosis of Rat Sertoli Cellsinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleinfo:eu-repo/semantics/openAccessreponame:Repositório Institucional da UNIFESPinstname:Universidade Federal de São Paulo (UNIFESP)instacron:UNIFESP11600/347262022-10-11 16:09:21.809metadata only accessoai:repositorio.unifesp.br:11600/34726Repositório InstitucionalPUBhttp://www.repositorio.unifesp.br/oai/requestopendoar:34652022-10-11T19:09:21Repositório Institucional da UNIFESP - Universidade Federal de São Paulo (UNIFESP)false |
dc.title.en.fl_str_mv |
17Beta-Estradiol Signaling and Regulation of Proliferation and Apoptosis of Rat Sertoli Cells |
title |
17Beta-Estradiol Signaling and Regulation of Proliferation and Apoptosis of Rat Sertoli Cells |
spellingShingle |
17Beta-Estradiol Signaling and Regulation of Proliferation and Apoptosis of Rat Sertoli Cells Royer, Carine [UNIFESP] CREB ESR1 estradiol/estradiol receptor GPER Gene regulation Sertoli cells Signal transduction |
title_short |
17Beta-Estradiol Signaling and Regulation of Proliferation and Apoptosis of Rat Sertoli Cells |
title_full |
17Beta-Estradiol Signaling and Regulation of Proliferation and Apoptosis of Rat Sertoli Cells |
title_fullStr |
17Beta-Estradiol Signaling and Regulation of Proliferation and Apoptosis of Rat Sertoli Cells |
title_full_unstemmed |
17Beta-Estradiol Signaling and Regulation of Proliferation and Apoptosis of Rat Sertoli Cells |
title_sort |
17Beta-Estradiol Signaling and Regulation of Proliferation and Apoptosis of Rat Sertoli Cells |
author |
Royer, Carine [UNIFESP] |
author_facet |
Royer, Carine [UNIFESP] Lucas, Thais Fabiana Gameiro [UNIFESP] Lazari, Maria de Fatima Magalhaes [UNIFESP] Porto, Catarina Segreti [UNIFESP] |
author_role |
author |
author2 |
Lucas, Thais Fabiana Gameiro [UNIFESP] Lazari, Maria de Fatima Magalhaes [UNIFESP] Porto, Catarina Segreti [UNIFESP] |
author2_role |
author author author |
dc.contributor.institution.none.fl_str_mv |
Universidade Federal de São Paulo (UNIFESP) |
dc.contributor.author.fl_str_mv |
Royer, Carine [UNIFESP] Lucas, Thais Fabiana Gameiro [UNIFESP] Lazari, Maria de Fatima Magalhaes [UNIFESP] Porto, Catarina Segreti [UNIFESP] |
dc.subject.eng.fl_str_mv |
CREB ESR1 estradiol/estradiol receptor GPER Gene regulation Sertoli cells Signal transduction |
topic |
CREB ESR1 estradiol/estradiol receptor GPER Gene regulation Sertoli cells Signal transduction |
description |
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. |
publishDate |
2012 |
dc.date.issued.fl_str_mv |
2012-04-01 |
dc.date.accessioned.fl_str_mv |
2016-01-24T14:27:00Z |
dc.date.available.fl_str_mv |
2016-01-24T14:27:00Z |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/article |
format |
article |
status_str |
publishedVersion |
dc.identifier.citation.fl_str_mv |
Biology of Reproduction. Madison: Soc Study Reproduction, v. 86, n. 4, 13 p., 2012. |
dc.identifier.uri.fl_str_mv |
https://repositorio.unifesp.br/handle/11600/34726 https://dx.doi.org/10.1095/biolreprod.111.096891 |
dc.identifier.issn.none.fl_str_mv |
0006-3363 |
dc.identifier.doi.none.fl_str_mv |
10.1095/biolreprod.111.096891 |
dc.identifier.wos.none.fl_str_mv |
WOS:000302767300011 |
identifier_str_mv |
Biology of Reproduction. Madison: Soc Study Reproduction, v. 86, n. 4, 13 p., 2012. 0006-3363 10.1095/biolreprod.111.096891 WOS:000302767300011 |
url |
https://repositorio.unifesp.br/handle/11600/34726 https://dx.doi.org/10.1095/biolreprod.111.096891 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.ispartof.none.fl_str_mv |
Biology of Reproduction |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.format.none.fl_str_mv |
13 |
dc.publisher.none.fl_str_mv |
Soc Study Reproduction |
publisher.none.fl_str_mv |
Soc Study Reproduction |
dc.source.none.fl_str_mv |
reponame:Repositório Institucional da UNIFESP instname:Universidade Federal de São Paulo (UNIFESP) instacron:UNIFESP |
instname_str |
Universidade Federal de São Paulo (UNIFESP) |
instacron_str |
UNIFESP |
institution |
UNIFESP |
reponame_str |
Repositório Institucional da UNIFESP |
collection |
Repositório Institucional da UNIFESP |
repository.name.fl_str_mv |
Repositório Institucional da UNIFESP - Universidade Federal de São Paulo (UNIFESP) |
repository.mail.fl_str_mv |
|
_version_ |
1802764247082467328 |