In Vivo Treatments with Fulvestrant and Anastrozole Differentially Affect Gene Expression in the Rat Efferent Ductules

In Vivo Treatments with Fulvestrant and Anastrozole Differentially Affect Gene Expression in the Rat Efferent Ductules

Author Oliveira Gomes, Gisele Renata Autor UNIFESP Google Scholar
Yasuhara, Fabiana Autor UNIFESP Google Scholar
Siu, Erica Rosanna Autor UNIFESP Google Scholar
Ferreira Fernandes, Sheilla Alessandra Autor UNIFESP Google Scholar
Werneck Avellar, Maria Christina Autor UNIFESP Google Scholar
Magalhaes Lazari, Maria Fatima Autor UNIFESP Google Scholar
Porto, Catarina Segreti Autor UNIFESP Google Scholar
Institution Universidade Federal de São Paulo (UNIFESP)
Inst Nacl Farmacol & Biol Mol
Abstract Estrogen plays a key role in maintaining the morphology and function of the efferent ductules We previously demonstrated that the antiestrogen fulvestrant markedly affected gene expression in the rat efferent ductules the mechanism of fulvestrant action to modulate gene expression may involve not only the blockade of ESR1 and ESR2 estrogen receptors, but also the activation of ESR1 and ESR2 when the receptors are tethered to AP 1 or SP1 transcription factors, or the activation of the G protein-coupled estrogen receptor 1 We therefore compared the effects of two strategies to interfere with estrogen action in the rat efferent ductules treatment with fulvestrant or with the aromatase inhibitor anastrozole Whereas fulvestrant markedly increased Mmp7 and Spp1, and reduced Npfx1 mRNA levels, no changes were observed with anastrozole Fulvestrant caused changes in epithelial morphology that were not seen with anastrozole Fulvestrant shifted MMP7 immunolocalization in the epithelial cells from the supranuclear to the apical region, this effect was less pronounced with anastrozole in vitro studies of S-35-methiomne incorporation showed that protein release was increased, whereas tissue protein content in the efferent ductules of fulvestrant-treated rats was decreased Although fulvestrant markedly affected gene expression, no changes were observed on AP 1 and SP1 DNA-binding activity the blockade of ESRs seems to be the major reason explaining the differences between both treatments At least some of the effects of fulvestrant appear to result from compensatory mechanisms activated by the dramatic changes caused by ESR1 blockade
Keywords estradiol receptor
gene regulation
male reproductive tract
Language English
Sponsor Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)
Grant number FAPESP: 2008/56564 1
Date 2011-01-01
Published in Biology of Reproduction. Madison: Soc Study Reproduction, v. 84, n. 1, p. 52-61, 2011.
ISSN 0006-3363 (Sherpa/Romeo, impact factor)
Publisher Soc Study Reproduction
Extent 52-61
Access rights Open access Open Access
Type Article
Web of Science ID WOS:000285658600009

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