The role of the androgen receptor in prostate development and benign prostatic hyperplasia: A review

Abstract

Benign prostatic hyperplasia (BPH) is a benign enlargement of the prostate in which incidence increases linearly with age, beginning at about 50 years old. BPH is a significant source of morbidity in aging men by causing lower urinary tract symptoms and acute urinary retention. Unfortunately, the etiology of BPH incidence and progression is not clear. This review highlights the role of the androgen receptor (AR) in prostate development and the evidence for its involvement in BPH. The AR is essential for normal prostate development, and individuals with defective AR signaling, such as after castration, do not experience prostate enlargement with age. Furthermore, decreasing dihydrotestosterone availability through therapeutic targeting with 5α-reductase inhibitors diminishes AR activity and results in reduced prostate size and symptoms in some BPH patients. While there is some evidence that AR expression is elevated in certain cellular compartments, how exactly AR is involved in BPH progression has yet to be elucidated. It is possible that AR signaling within stromal cells alters intercellular signaling and a “reawakening” of the embryonic mesenchyme, loss of epithelial AR leads to changes in paracrine signaling interactions, and/or chronic inflammation aids in stromal or epithelial proliferation evident in BPH. Unfortunately, a subset of patients fails to respond to current medical approaches, forcing surgical treatment even though age or associated co-morbidities make surgery less attractive. Fundamentally, new therapeutic approaches to treat BPH are not currently forthcoming, so a more complete molecular understanding of BPH etiology is necessary to identify new treatment options.

Human Prostate Epithelial Cells Activate the AIM2 Inflammasome upon Cellular Senescence: Role of POP3 Protein in Aging-Related Prostatic Inflammation

“…Serum androgen levels decrease in men with aging [36,37]. Further, androgen receptor levels increase in PrECs in certain parts of the prostate [37].…”

“…Serum androgen levels decrease in men with aging [36,37]. Further, androgen receptor levels increase in PrECs in certain parts of the prostate [37]. Therefore, our observations that senescent PrECs that activated type I IFN signaling expressed higher basal levels of the AR (Figure 1B) and activation of androgen receptor in human PrECs increased the levels of POP3 protein (Figure 2) and increased levels of POP3 in PrECs inhibited cytosolic DNA-induced activation of the AIM2 inflammasome activity (Figure 3) support the idea that aging-related reduced serum levels of androgens in men contribute to a decrease in the levels of POP3 protein in PrECs, thus leading to an increase in activation of the AIM2 inflammasome.…”

TNF Blockade Reduces Prostatic Hyperplasia and Inflammation while Limiting BPH Diagnosis in Patients with Autoimmune Disease

“…The contributing role(s) of the androgen receptor in BPH is not fully understood, and the involvement of androgen receptor signaling in prostatic inflammation may contribute to this complexity (48,49). Reduced circulating androgen levels in aging men might contribute to .…”

“…The immunosuppressive function of androgens has been reported in numerous studies ( 32 ). The contributing role(s) of the androgen receptor in BPH is not fully understood, and the involvement of androgen receptor signaling in prostatic inflammation may contribute to this complexity ( 48, 49 ). Reduced circulating androgen levels in aging men might contribute to increased inflammation in BPH, but whether the increase in inflammation is in response to a stimulus (e.g.…”

The Effect of Zinc, Selenium, and Their Combined Supplementation on Androgen Receptor Protein Expression in the Prostate Lobes and Serum Steroid Hormone Concentrations of Wistar Rats

“…However, no studies have so far exhaustively examined the influence of both Zn and Se on the proper functioning of the prostate. While single studies have evaluated their individual effects on hormone levels and prostate cell proliferation or AR expression in the prostate, they have not been studied in combination [31]. Hence, it cannot be excluded that concurrent administration of Zn and Se may be not beneficial.…”