Intracellular signaling pathways involved in the relaxin-induced proliferation of rat Sertoli cells

dc.contributor.authorNascimento, Aline Rosa [UNIFESP]
dc.contributor.authorPimenta, Maristela Taliari [UNIFESP]
dc.contributor.authorLucas, Thais Fabiana Gameiro [UNIFESP]
dc.contributor.authorRoyer, Carine [UNIFESP]
dc.contributor.authorPorto, Catarina Segreti [UNIFESP]
dc.contributor.authorLazari, Maria de Fatima Magalhaes [UNIFESP]
dc.contributor.institutionUniversidade Federal de São Paulo (UNIFESP)
dc.date.accessioned2016-01-24T14:27:42Z
dc.date.available2016-01-24T14:27:42Z
dc.date.issued2012-09-15
dc.description.abstractRegulation of Sertoli cell number is a key event to determine normal spermatogenesis. We have previously shown that relaxin and its G-protein coupled receptor RXFP1 are expressed in rat Sertoli cells, and that relaxin stimulates Sertoli cell proliferation. This study examined the mechanisms underlying the mitogenic effect of relaxin in a primary culture of Sertoli cells removed from testes of immature rats. Stimulation with exogenous relaxin increased Sertoli cell number and the expression of the proliferating cell nuclear antigen (PCNA), but did not affect them RNA level of the differentiation markers cadherins 1 and 2. Relaxin-induced Sertoli cell proliferation was blocked by inhibition of MEK/ERK1/2 or PI3K/AKT pathways, but not by inhibition of PKC or EGFR activity. Relaxin induced a rapid and transient activation of ERK1/2 phosphorylation, which was MEK and SRC-dependent, and involved upstream activation of G(i). AKT activation could be detected 5 min after relaxin stimulation, and was still detected after 24 h of stimulation with relaxin. Relaxin-induced AKT phosphorylation was G(i)- but not PKA-dependent, and it was blocked by both PI3K and MEK inhibitors. in conclusion, the mitogenic effect of relaxin in Sertoli cell involves coupling to G(i) and activation of both MEK/ERK1/2 and PI3K/AKT pathways. (c) 2012 Elsevier B.V. All rights reserved.en
dc.description.affiliationUniversidade Federal de São Paulo, Sect Expt Endocrinol, Dept Pharmacol, Escola Paulista Med, São Paulo, Brazil
dc.description.affiliationUnifespUniversidade Federal de São Paulo, Sect Expt Endocrinol, Dept Pharmacol, Escola Paulista Med, 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: 2008/57239-7pt
dc.format.extent283-291
dc.identifierhttps://dx.doi.org/10.1016/j.ejphar.2012.07.021
dc.identifier.citationEuropean Journal of Pharmacology. Amsterdam: Elsevier B.V., v. 691, n. 1-3, p. 283-291, 2012.
dc.identifier.doi10.1016/j.ejphar.2012.07.021
dc.identifier.issn0014-2999
dc.identifier.urihttps://repositorio.unifesp.br/handle/11600/35274
dc.identifier.wosWOS:000307815800035
dc.language.isoeng
dc.publisherElsevier B.V.
dc.relation.ispartofEuropean Journal of Pharmacology
dc.rightsinfo:eu-repo/semantics/restrictedAccess
dc.rights.licensehttp://www.elsevier.com/about/open-access/open-access-policies/article-posting-policy
dc.subjectRelaxinen
dc.subjectRXFP1en
dc.subjectSertoli cellen
dc.subjectProliferationen
dc.subjectERK1/2en
dc.subjectPI3K/AKTen
dc.titleIntracellular signaling pathways involved in the relaxin-induced proliferation of rat Sertoli cellsen
dc.typeinfo:eu-repo/semantics/article
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