Mapeamento do receptor de vitamina D (VDR) no complexo prostático deratos Wistar durante o envelhecimento

Abstract

The prostate is regulated by a complex interplay of endocrine and paracrine signals, including Vitamin D that acts via its specific VDR receptor, carrying out diverse functions such as calcium homeostasis, anti-inflammatory and anti-carcinogenic actions. Despite several studiessuggesting that age is an important risk factor for development of benign prostatic hyperplasia and prostate cancer, both conditions of great clinical relevance, and that low levels of vitamin D commonly found in aging might contribute to the occurrence and progression of these diseases, little is known about the age-dependent variation in tissue concentrations of VDR. In addition, most of the studies concerning VDR expression in the prostate was conducted in vitro. Therefore, our aim was to evaluate the expression pattern of VDR in the prostatic complex of adult Wistar rats, during aging (3, 6, 12, 18 and 24 months of age), correlating these results with the vitamin D levels and the development of punctual histopathological changes common in advancing age. The immunohistochemical assays revealed that VDR is widely distributed throughout the prostatic complex of Wistar rats, as an intense positivity was observed for this receptor in nuclei of both epithelial and stromal cells. Higher intensity of VDR immunoreactivity was detected in nuclei of basal cells in the glandular epithelium compared to the luminal cells. Significant increase in VDR levels was detected after 12 months of age, paralleling a marked reduction of about 2.8-fold in the plasma concentration of 25(OH)D. The immunostaining intensity for VDR-positive cells in areas of epithelial atrophy, hyperplasia or prostate intraepithelial neoplasia (PIN), which are considered morphologicalalterations commonly found in the prostatic epithelium of senile rats (18 and 24 months), was similar to that observed for the adjacent normal epithelium. However, it is noteworthy that the proportion of cells VDR-negative was significantly higher in PIN areas compared to normalepithelium. Taken together with the literature, these relevant results support: a) the existence of age-dependent variation in the vitamin D endocrine system; b) the hypothesis that vitamin D is a putative hormone acting in prostate, including the normal gland; c) the need to consider the amount of VDR protein to interpret the magnitude of vitamin D signaling in target cells, which might be inversely related to circulating levels of 25(OH)D; d) a possible involvement of a punctual disorder in the VDR pathway and the prostate carcinogenesis, since the higher number of VDR-negative cells was observed in PIN areas, which are considered premalignant lesions in the prostate.