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8 September 2010 In Vivo Treatments with Fulvestrant and Anastrozole Differentially Affect Gene Expression in the Rat Efferent Ductules
Gisele Renata Oliveira Gomes, Fabiana Yasuhara, Erica Rosanna Siu, Sheilla Alessandra Ferreira Fernandes, Maria Christina Werneck Avellar, Maria Fatima Magalhaes Lazari, Catarina Segreti Porto
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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 Nptx1 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 35S-methionine 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.

Gisele Renata Oliveira Gomes, Fabiana Yasuhara, Erica Rosanna Siu, Sheilla Alessandra Ferreira Fernandes, Maria Christina Werneck Avellar, Maria Fatima Magalhaes Lazari, and Catarina Segreti Porto "In Vivo Treatments with Fulvestrant and Anastrozole Differentially Affect Gene Expression in the Rat Efferent Ductules," Biology of Reproduction 84(1), 52-61, (8 September 2010). https://doi.org/10.1095/biolreprod.110.085340
Received: 13 April 2010; Accepted: 1 August 2010; Published: 8 September 2010
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KEYWORDS
estradiol receptor
gene regulation
male reproductive tract
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