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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

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

Full text
Author(s):
Augusto, Taize M. [1] ; Rosa-Ribeiro, Rafaela [1] ; Carvalho, Hernandes F. [1]
Total Authors: 3
Affiliation:
[1] State Univ Campinas UNICAMP, Dept Anat Cell Biol Physiol & Biophys, Inst Biol, BR-13083863 Campinas, SP - Brazil
Total Affiliations: 1
Document type: Journal article
Source: Histochemistry and Cell Biology; v. 136, n. 5, p. 609-615, NOV 2011.
Web of Science Citations: 6
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. (AU)

FAPESP's process: 09/16150-6 - Androgen regulation, sinalization and cellular interactions in prostate development, physiology and regression
Grantee:Hernandes Faustino de Carvalho
Support Opportunities: Research Projects - Thematic Grants