Keywordsprostate; prostate cancer; estrogens; estradiol; estrogen receptor Estrogens have significant direct and indirect effects on prostate gland development and homeostasis and have been long suspected in playing a role in the etiology of prostatic diseases. Direct effects are mediated through prostatic estrogen receptors alpha (ERα) and beta (ERβ) with expression levels changing over time and with disease progression. The present review examines the evidence for a role of estrogens and specific estrogen receptors in prostate growth, differentiation and disease states including prostatitis, benign prostatic hyperplasia (BPH) and cancer and discusses potential therapeutic strategies for growth regulation via these pathways.
Estrogens in the Male and Effects on the Prostate GlandWhile low levels of circulating estrogens are present throughout life in males, there are two time periods, during in utero development and aging, when males are exposed to relatively higher levels of circulating estradiol which have been shown to impact the prostate gland. In addition, estrogens may be produced locally within the prostate via conversion of testosterone to 17β-estradiol by aromatase expressed within the prostate stroma [1,2], thus estrogen action in the prostate may occur independent of serum levels of this steroid.During the third trimester of in utero development in humans, rising maternal estradiol and declining fetal androgen production result in an elevated estrogen/testosterone (E/T) ratio. This relative increase in estradiol has been shown to directly stimulate extensive squamous metaplasia within the developing prostatic epithelium which regresses immediately after birth when estrogen levels rapidly decline [3,4]. Although the natural role for estrogens during prostatic development is unclear, it has been proposed that excessive estrogenization during prostatic development may contribute to the high incidence of BPH and prostatic carcinoma currently observed in the aging male population [5]. African-American men have a two-fold increased risk of prostatic carcinoma as compared to their Caucasian counterparts and it has been suggested that this is related, in part, to elevated levels of maternal estrogens during early gestation in this population [6,7]. Indicators of pregnancy estrogen levels such as length of Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers