Avaliação do perfil de proliferação celular na próstata dorsal de ratos Wistar em envelhecimento

Abstract

The prostate plays important role in the physiology of the male reproductive system and fertility. This organ is also target of important diseases such as benign hyperplasia and adenocarcinoma, the latter being the type of non-skin cancer that affects more men in Brazil and worldwide. The disease targets specially the peripheral zone of the human prostate, which is the homologous region to the rat dorsal lobe of the prostate, being also affected by spontaneous or induced neoplasias. The prostate is a classic androgen-dependent tissue, however, it is also influenced by estrogens and their ER receptors. The estrogen system is involved in the differentiation and growth of the gland as well as in their pathologies, illustrated by the fact that the ER expression is gradually silenced with the progress of the malignant changes. Age is a risk factor for prostate cancer, considering that the incidence and mortality increase in the elderly. Corroborating these data, preliminary studies indicate reduction of ER in different prostatic lobes of old rats, in places closely related to proliferative changes. Considering that ER have pro-apoptotic, anti-proliferative and pro-differentiation functions, it is possible that its silencing may be related to an imbalance between cell proliferation and death in these pathological conditions. Thus, the aim of this study was to determine the profile of cell proliferation in the dorsal prostate (DP) of young to senescent Wistar rats (3, 6, 12, 18 and 24 months), based on two routine markers, MCM7 and PCNA. Histopathological analysis revealed that the animals at 12 months onward presents prostatic hyperplasia and disordered regions of stratified epithelium, suggestive of prostatic intraepithelial neoplasia (PIN). Immunohistochemical analysis of MCM7 and PCNA revealed that the DP of young adult animals is usually little proliferative. However, during aging, there is a reduction of cellular proliferation in general tissue but increases the occurrence of PIN regions, which are intensely marked by MCM7, but not by PCNA, indicating a higher specificity of the first marker. The PIN areas are the same that have reduced ER expression, thus confirming a possible interrelationship between the silencing of this receptor with malignant or pre-malignant conditions of the prostate.