Changes in estrogen receptor ERβ (ESR2) expression without changes in the estradiol levels in the prostate of aging rats

Abstract

Although the prostate is androgen-dependent, it is also influenced by estrogens, which act via the estrogen receptors ERα and ERβ. In the prostate, ERβ is highly expressed in the epithelium and appears to participate in the regulation of cell proliferation, apoptosis and differentiation. Evidence shows that ERβ is decreased in malignant prostate, suggesting that it plays an important role in protecting this tissue. Despite the relationship between reductions in ERβand abnormal growth of the gland, little is known about the age-dependent variation of this receptor. Therefore, we aimed to investigate ERβ expression in the prostatic lobes of aging Wistar rats (3 to 24 months). Histopathological alterations, including hyperplasia, intraluminal concretions, nuclear atypia and prostate intraepithelial neoplasias (PIN), were observed in the prostates of aging rats. Epithelial proliferation led to cribriform architecture in some acini, especially in the ventral prostate (VP). In the VP, areas of epithelial atrophy were also observed. Furthermore, in the lateral prostate, there was frequent prostatitis. Immunohistochemistry revealed that the expression of ERβ is reduced in specific areas related to PIN, atrophic abnormalities and cellular atypia in the prostate epithelium of senile rats. Corroborating the involvement of the receptor with proliferative activity, the punctual reduction in ERβ paralleled the increase in cell proliferation especially in areas of PIN and nuclear atypies. The decrease in ERβ reactivity occurred in a hormonal milieu characterized by a constant concentration of estradiol and decreased plasmatic and tissue DHT. This paper is a pioneering study that reveals focal ERβ reduction in the prostate of aging rats and indicates a potential disorder in the ERβ pathway. These data corroborate previous data from humans and dogs that silencing of this receptor may be associated with premalignant or malignant conditions in the prostate.