Alterações na expressão dos receptores de estrógenos ERβ na próstata ventral de ratos em envelhecimento

Abstract

The prostate is one of the main targets for cancer development in men. The prostatic adenocarcinoma is the most common type of non-cutaneous cancer in Brazil and worldwide. It is known that age is an important risk factor in this pathology and that its frequency and mortality increase significantly after 50 years old. Although the prostate is an androgen dependent organ, an increasing body of evidences point out that estrogens also participate on the growing and differentiation of this organ, as well as in its pathologies. Estrogens act through the binding to specific nuclear receptors named ERα and ERβ. ERα is expressed only in some cells of the prostatic stroma, whereas ERβ is highly expressed in the glandular epithelium, playing important pro-apoptotic, anti-proliferative and pro-differentiation roles. Several studies suggest that the expression of ERβ is drastically reduced during the progression of prostatic adenocarcinoma, as in 75% of the cases the receptor is not expressed in the affected tissue. The reintroduction of ERβ in the malignant cells promotes the reduction in proliferation and invasive ability of these cells. In despite of this relationship between the decrease in ERβ expression and the abnormal growing of the prostatic tissue common during aging, little is known about the age-dependent variation in the expression of this receptor in the prostate. Therefore, the aim of this study is to investigate whether ERβ expression is altered with aging in the ventral prostate of Wistar rats of different ages (3, 6, 12, 18, 24 months). Remarkable morphological alterations were observed in the ventral prostate of aging rats, including intense atrophy, hyperplasia, focuses of intraepithelial proliferation, suggestive of intraepithelial neoplasia, as well as the accumulation of cytoplasmatic mucoid material and nuclear atipies. The analysis of ERβ expression by Western blotting did not show differences in the expression of this protein among prostates at different ages. On the other hand, the immunohistochemistry revealed that in senile animals there were alterations in the expression of this receptor in specific areas, related to the intraepithelial proliferative and atrophic abnormalities. These relevant results add to previous findings about reduced ERβ expression in pre-malignant and malignant disorders in human and dog prostates, suggesting an association of prostatic pathologies with a putative disorder in the pathway mediated by ERβ, which is considered as an anti-proliferative and pro-differentiation factor, consisting in protector against cancer. The results of the present study are of remarkable interest, since information about the expression of ERβ in the aging prostate was not found in any other species.