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Type: Artigo de periódico
Title: Neonatal exposure to high doses of 17 beta-estradiol results in inhibition of heparanase-1 expression in the adult prostate
Author: Augusto, TM
Rosa-Ribeiro, R
Carvalho, HF
Abstract: Heparanase-1 (HPSE-1) is an endoglycosidase that cleaves heparan sulfate. The physiological functions of HPSE-1 include embryo development, hair growth, wound healing, tumor growth, angiogenesis, metastasis, and inflammation. HPSE-1 expression was found to increase temporarily in the rat ventral prostate (VP) after castration. The promoter region of the Hpse-1 gene has estrogen-responsive elements, suggesting that the gene is regulated by estrogens. In this study, we investigated the expression of HPSE-1 in the VP of 90-day-old rats after neonatal exposure to a high dose of 17 beta-estradiol. HPSE-1 was not found by immunohistochemistry in the epithelium of estrogenized animals. To determine whether inhibition of Hpse-1 expression in the epithelium was due to pre- or post-transcriptional regulation, epithelial cells were isolated by centrifugation in Percoll gradient and the presence of Hpse-1 mRNA was investigated by RT-PCR. Hpse-1 mRNA was not detected in the estrogenized animals. Considering that Hpse-1 transcription could be inhibited by DNA methylation, we used the methylation-sensitive restriction enzyme HpaII and PCR to show that a single CCGG site at position +185 was more frequently methylated in the epithelium of estrogenized than in control animals. Immunohistochemistry for 5-methylcytidine revealed that the epithelial cell nuclei in estrogenized animals were heavily methylated. These results suggest that Hpse-1 expression was blocked in the epithelial cells of the VP, by estrogen imprinting by a pre-transcriptional mechanism involving DNA methylation.
Subject: DNA methylation
Epigenetic regulation
Estrogen imprinting
Country: EUA
Editor: Springer
Citation: Histochemistry And Cell Biology. Springer, v. 136, n. 5, n. 609, n. 615, 2011.
Rights: fechado
Identifier DOI: 10.1007/s00418-011-0860-9
Date Issue: 2011
Appears in Collections:Unicamp - Artigos e Outros Documentos

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