Estrogen-regulated development and differentiation of the prostate.

Both androgens and estrogens play a significant role in the prostate and are critical for normal prostate growth and development, as well as the maintenance of adult prostatic homeostasis throughout life. It is the balance of these two hormones, rather than each individually, that is important for prostatic development and differentiation. Estrogen action is mediated by the estrogen receptors, ERalpha and ERbeta. ERalpha is expressed throughout the prostatic tissue during fetal and early neonatal life, and if activated inappropriately, produces late-life disease, including inflammation and emergence of pre-malignant pathologies. In contrast, ERbeta expression is initiated after ERalpha, is localized primarily to the epithelium, and appears to be important during later periods of development such as puberty and adulthood, acting to regulate cellular proliferation and differentiation in the adult tissue. Therefore, there is also a spatial and temporal balance between ERalpha and ERbeta that is critical for development. Together with the shifting balance between androgens and estrogens themselves, the subtle, yet critical, balance between the activity of ERalpha and ERbeta is what ultimately determines the response of the prostate to estrogen, and is crucial for prostate health.