Changes in the endocrine environment of the human prostate transition zone with aging: simultaneous quantitative analysis of prostatic sex steroids and comparison with human prostatic histological composition

Abstract

Background: It is well-known that the incidence of benign prostatic hyperplasia (BPH) increases with aging. The age-dependent changes in the ratio of serum sex steroid concentrations may play a role in BPH development. To clarify the relationship between the prostatic tissue concentrations of these steroids and age, we established a precise method of simultaneous quantitative analysis for prostatic sex steroids and used this method to investigate the tissue concentrations of three major sex steroids (testosterone, dihydrotestosterone, and estradiol) in the human prostate.

Methods: The methodology for the simultaneous quantitative analysis of prostatic sex steroids was established using castrated rat prostatic tissue, coupled with internal standards, for androgen-deprived medium, and the validation of the method was examined. Human prostatic tissues were collected during surgery and immediately frozen at -70 degrees C. Using our method, the steroidal fractions were extracted, purified, and quantified. The proportions of stroma, epithelium, and glandular lumen were measured on each histological specimen, using an image analyzer.

Results: The validation tests showed that our method of quantitative analysis was precise and sensitive enough for the quantification of testosterone, dihydrotestosterone, and estradiol in the prostate. In humans, the prostatic dihydrotestosterone concentration decreased with age, but the concentrations of testosterone and estradiol showed no relation with age. Therefore, the ratio of estradiol to dihydrotestosterone concentration (E2/DHT) in prostate increased with age. The E2/DHT ratio showed a significant positive correlation with the proportion of stroma.

Conclusions: The age-dependent decrease in prostatic dihydrotestosterone and constant estradiol concentration lead to a relatively estrogen-dominant environment compared to that at younger ages. We assume that this relatively estrogen-dominant status induces stromal proliferation by some mechanism and leads to the development of BPH.