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(Referência obtida automaticamente do Web of Science, por meio da informação sobre o financiamento pela FAPESP e o número do processo correspondente, incluída na publicação pelos autores.)

Neonatal exposure to high doses of 17 beta-estradiol results in inhibition of heparanase-1 expression in the adult prostate

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Autor(es):
Augusto, Taize M. [1] ; Rosa-Ribeiro, Rafaela [1] ; Carvalho, Hernandes F. [1]
Número total de Autores: 3
Afiliação do(s) autor(es):
[1] State Univ Campinas UNICAMP, Dept Anat Cell Biol Physiol & Biophys, Inst Biol, BR-13083863 Campinas, SP - Brazil
Número total de Afiliações: 1
Tipo de documento: Artigo Científico
Fonte: Histochemistry and Cell Biology; v. 136, n. 5, p. 609-615, NOV 2011.
Citações Web of Science: 6
Resumo

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. (AU)

Processo FAPESP: 09/16150-6 - Regulação androgênica, sinalização e interações celulares no desenvolvimento, fisiologia e regressão prostática
Beneficiário:Hernandes Faustino de Carvalho
Linha de fomento: Auxílio à Pesquisa - Temático