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This Article Full Text Full Text (PDF) [Supplemental Data] All Versions of this Article: 78/1/101    most recent biolreprod.107.063909v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Lucas, T. F.G Articles by Lazari, M. F. M Search for Related Content PubMed PubMed Citation Articles by Lucas, T. F.G Articles by Lazari, M. F. M Agricola Articles by Lucas, T. F.G Articles by Lazari, M. F. M

17Beta-Estradiol Induces the Translocation of the Estrogen Receptors ESR1 and ESR2 to the Cell Membrane, MAPK3/1 Phosphorylation and Proliferation of Cultured Immature Rat Sertoli Cells¹

Section of Experimental Endocrinology,³ Department of Pharmacology, and Department of Biochemistry,⁴ Universidade Federal de São Paulo, Escola Paulista de Medicina, São Paulo 04044-020, Brazil Department of Morphology,⁵ Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais 31270-901, Brazil

ABSTRACT

The aim of the present study was to determine the mechanisms involved in estrogen actions in cultured rat Sertoli cells. RT-PCR detected transcripts for the estrogen receptors ESR1 and ESR2 in cultured immature Sertoli cells and in the testis of 15-, 28-, and 120-day-old rats. The expression of ESR1 and ESR2 was confirmed in Sertoli cells by immunofluorescence and Western blot. Immunohistochemistry with cryosections of testes from immature and adult rats revealed that ESR1 is present in Sertoli, Leydig, and some peritubular myoid cells, and ESR2 is present in multiple cell types, including germ cells. Treatment of Sertoli cells with 17beta-estradiol (E₂) induced a translocation of ESR1 and ESR2 to the plasma membrane and a concomitant phosphorylation of MAPK3/1. Both effects reached a maximum after 10 min and were blocked by PP2, an inhibitor of the SRC family of protein tyrosine kinases, and by the antiestrogen ICI 182,780 (ICI). MAPK3/1 phosphorylation was also decreased in the presence of AG 1478, an inhibitor of the epidermal growth factor receptor (EGFR) kinase, and in the presence of MAP2K1/2 inhibitor UO126. Treatment with E₂ for 24 h increased the incorporation of [methyl-³H]thymidine, which was blocked by ICI. These results indicate that E₂ activates an SRC-mediated translocation of estrogen receptors to the plasma membrane, which results in the activation of EGFR and the mitogen-activated protein kinase signaling pathway. In addition, activation of ESR1 and/or ESR2 by E₂ is involved in proliferation of immature Sertoli cells. The estrogen actions in Sertoli cells might be a key step mediating cellular events important for spermatogenesis and fertility.

estradiol, estradiol receptor, kinases, mechanisms of hormone action, Sertoli cells

¹Supported by Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP, grant 2004/01152-0, to C.S.P.). Research fellowship (C.S.P.) was supported by Conselho Nacional de Desenvolvimento Cientifico e Tecnológico, CNPq. Doctoral fellowships supported by CNPq (T.F.G.L.) and FAPESP (E.R.S.). Master fellowship supported by Coordenação de Aperfeiçoamento de Pessoal de Nível Superior, CAPES (C.A.E.).

Correspondence: ²Maria Fatima M. Lazari, Section of Experimental Endocrinology, Department of Pharmacology, Universidade Federal de São Paulo, Escola Paulista de Medicina, Rua Três de maio 100, INFAR, Vila Clementino, São Paulo, SP 04044-020, Brazil. FAX: 5511 5576 4448; e-mail: lazari{at}farm.epm.br