The Influence of Oestradiol on the Metabolism of Androgens by Human Prostatic Tissue

Abstract

The uptake and metabolism of testosterone, androstenedione and 5alpha-dihydrotestosterone (DHT) by human benign hyperplastic prostates and prostatic carcinomas have been measured in organ culture. DHT was a major metabolite of both testosterone and androstenedione in the benign tissue and the androstanediols were the principal metabolites of DHT. Over half the carcinomas produced less DHT from testosterone than the benign hyperplastic prostates, and carcinomas from the oldest patients showed an enhancement of 17beta-hydroxysteroid dehydrogenation. There was no relationship between these differences in metabolism and the degree of differentiation of the carcinomas. Oestradiol decreased the production of DHT from both testosterone and androstenedione and, at low androgen concentrations, increased the production of androstanediols from testosterone, androstenedione and DHT. Uptake of DHT, but not of the other two androgens, was stimulated by oestradiol.

RELATIONSHIPS BETWEEN OESTRADIOL-17β, TESTOSTERONE, DIHYDROTESTOSTERONE AND 5α-Androstane-3α,17β-Diol IN HUMAN BENIGN HYPERTROPHY AND CARCINOMA OF THE PROSTATE

“…Similar studies performed by Bard & Lasnitzki (1977) have shown that oestradiol is capable of decreasing the formation of DHT from testosterone. The higher mean level of tissue oestradiol in cancerous tissue than in hypertrophie tissue and its negative correlation with tissue concentrations of DHT and 5a-androstane-3a,17ß-diol in patients with BPH could also imply that this oestrogen exerts some actions on the regulation of the two main enzymes, i.e.…”

“…However,we have found that in benign tissues, DHT and androstanediols are the main metabolites of testosterone, whereas androstenedione represents the major metabolite in neoplastic tissue (Ghanadian, Masters & Smith, 1979). Furthermore, oestradiol has been shown in vitro to inhibit the activities of 5a-reductase (Shimazaki, Kurihara, Ito & Shida, 1965) and the 3a(ß)-hydroxysteroid dehydrogenase in BPH and neoplastic tissues (Jenkins & McCaffery, 1974;Tan, Antonipillai & Murphy, 1974;Bard & Lasnitzki, 1977). All these investigations emphasize the significance of the combined effects of androgen metabolites and oestradiol in the prostate.…”

Androgen, estrogen, and progesterone receptor contents and serum hormone profiles in patients with benign hypertrophy and carcinoma of the prostate

“…This observation strongly suggests that there was an estrogen-dependent positive regulation of the ARC as reported earlier for the canine prostate [ 19,201. Alternatively, it is also pos-Androgen receptor. sible that estrogens act either via hypophyseal-gonadal axis leading to low levels of plasma testosterone [21,22] or by suppressing the production of dihydrotestosterone from testosterone [23] so that the ARC depletion rate is reduced or stopped. Our results on the PCA group are in apparent contrast with those of Ekman et al [24] and Concolino et al [25] who have found nearly 80% of the patients to be ARC positive, even though they did not receive any hormone therapy.…”

A Morphological Study on the Effect of Cyproterone Acetate on Human Prostatic Carcinoma

“…In contrast, poorly differentiated prostatic neoplasms were markedly deficient in their capacity to convert testosterone to Sa-DHT. Bard & Lasnitzki (1977) found on the other hand, no relationship between androgen metabolism and the degree of differentiation of the carcinoma. In their study, prostatic carcinoma produced less Sa-DHT from testosterone than the benign hyperplastic prostate in agreement with the reports of Prout et al (1976) and Djoeseland et al (1977).…”