Impacto da exposição ao DHEA-S na próstata de gerbilos senis: explorando mecanismos hormonais e implicações terapêuticas

Abstract

The prostate is an essential gland of the male reproductive system, whose main function is to produce secretions that promote sperm viability. Its origin is associated with evolution and sperm competition. With aging, the gland becomes more susceptible to diseases such as benign prostatic hyperplasia (BPH) and prostate cancer (PCa), conditions that are highly prevalent among elderly men. Although commonly associated with the male sex, prostatic structures are also present in females of some mammalian species. The prostate has a complex architecture composed of epithelial and stromal compartments, which are mainly regulated by hormones such as androgens and estrogens. During aging, there is a decline in hormone levels such as testosterone and DHEA-S (dehydroepiandrosterone sulfate), which can impair prostatic homeostasis and contribute to the development of pathologies. DHEA-S, mainly produced by the adrenal glands, can be converted into testosterone, DHT, or estrogens, directly influencing hormone receptors in the prostate. Supplementation with DHEA-S has been studied for its chemopreventive and metabolic potential, although it also presents risks, such as liver alterations and hormonal imbalances. This study analyzed the effects of DHEA-S administration in aged Mongolian gerbils (18 months old), including 10 males and 10 females, divided into control and treated groups. The dose was 60 mg/kg, administered subcutaneously once a week for five weeks. Biometric, hormonal, histological, and immunohistochemical analyses were performed, as well as quantification of prostatic lipofuscin, a marker of cellular senescence. Serum DHEA-S levels increased in both sexes, but only females showed an increase in body weight after treatment. Morphologically, treated males showed a reduction in epithelial thickness and in the number of clear cells, but no changes in the smooth muscle layer (SML). In females, dysplasia and metaplasia were observed, along with increased glandular secretions and greater accumulation of lipofuscin, suggesting an intensified secretory response. Androgen receptor expression was higher in males, but its presence in the epithelium decreased after treatment, while it increased in the SML. Estrogen receptor alpha showed increased epithelial staining only in treated females, with a reduction in the SML. Estrogen receptor beta showed no significant changes. The enzyme 5α-reductase, important in the conversion of testosterone to DHT, had increased expression in males after DHEA-S treatment. Thus, this study demonstrated that DHEA-S affects male and female prostates differently, with more marked effects in females, particularly related to secretory activity and cellular changes. These findings highlight the role of the tissue microenvironment and intracrine mechanisms in the hormonal modulation response during aging.