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- Title
Neonatal exposure to high doses of 17β-estradiol results in inhibition of heparanase-1 expression in the adult prostate.
- Authors
Augusto, Taize; Rosa-Ribeiro, Rafaela; Carvalho, Hernandes
- 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 17β-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.
- Subjects
NEWBORN infants; DRUG dosage; ESTRADIOL; ENZYME inhibitors; GENE expression; PROSTATE; ENDOGLYCOSIDASES; GENETIC regulation; IMMUNOHISTOCHEMISTRY; REVERSE transcriptase polymerase chain reaction
- Publication
Histochemistry & Cell Biology, 2011, Vol 136, Issue 5, p609
- ISSN
0948-6143
- Publication type
Article
- DOI
10.1007/s00418-011-0860-9