Concentrations of 3β‐hydroxy androgens in epithelium and stroma of benign hyperplastic and normal human prostate

Abstract

Androgen metabolites with 3 beta-hydroxy configuration--ie, dehydroepiandrosterone (3 beta-hydroxy-5-androsten-17-one, DHEA), 5-androstene-3 beta-17 beta-diol (A-Diol), and 5 alpha-androstane-3 beta, 17 beta-diol (3 beta-Diol)--were measured by radioimmunoassay in the homogenate, in the mechanically separated epithelium and stroma, and in the nuclear fractions of epithelium and stroma of benign hyperplastic (BPH) and normal human prostatic tissue, in muscle homogenates and in plasma. The main results were: 1) Mean prostatic DHEA, A-Diol and 3 beta-Diol were 6-7 times as high as plasma values (1 g = 1 ml). Compared to muscle, prostatic values were more than tenfold higher. 2) The values in homogenates of BPH and normal prostate were not statistically different (pmol/mg DNA, mean +/- SEM, BPH: DHEA 46.8 +/- 7.2, n = 11; A-Diol 5.7 +/- 1.2, n = 12; 3 beta-Diol 3.7 +/- 0.6, n = 13; normal prostate: DHEA 56.0 +/- 5.5, n = 2; A-Diol 7.4 +/- 2.4, n = 5; 3 beta-Diol 5.8 +/- 1.7, n = 5). 3) In the nuclear fractions of epithelium and stroma the values were low compared to the homogenates and could not be discriminated from unspecific retention. Although we could not demonstrate either a specific retention of the 3 beta-hydroxysteroids in the nuclei or conclusive differences in steroid accumulation between epithelium and stroma of BPH and normal prostate, which could explain the development of the disease, the high levels in the tissue particularly of A-Diol would be compatible with estrogenic action at the prostate level.

Sex steroid hormones in pairs of tumor and serum from breast cancer patients and pathobiological role of androstene‐3β, 17β‐diol

“…Both Aenediol and Aanediol have been reported to have estrogenic function, and higher affinity for ER-b than ER-a. (16,17) These have been reported to be present in the prostate at a high concentration, (38,39) and have also attracted breast cancer researchers; (18,40,41) however, Aanediol was revealed to be present in extremely low concentrations both in the serum and cancerous tissue. In contrast, Aenediol was revealed to be abundant both in the serum and tumor tissue.…”

cyp7b1 catalyses the 7α-hydroxylation of dehydroepiandrosterone and25-hydroxycholesterol in rat prostate

“…High concentrations of DHEA and A\enediol (6 -7 times as high as plasma values) have been found in the human prostate gland [31]. Moreover, the prostatic DHEA concentration is 10-fold higher than the concentration of A\anediol in the same tissue [31]. These data suggest that 3β-steroids, such as DHEA and A\enediol (both substrates for cyp7b1), may selectively accumulate in the prostate.…”

“…These kinetic parameters demonstrate clearly the presence of a steroid 7α-hydroxylase activity in the prostate that catalyses the 7α-hydroxylation of A\enediol, DHEA, E # , A\anediol and 25-HOChol. High concentrations of DHEA and A\enediol (6 -7 times as high as plasma values) have been found in the human prostate gland [31]. Moreover, the prostatic DHEA concentration is 10-fold higher than the concentration of A\anediol in the same tissue [31].…”

Sex steroids in the tumor microenvironment and prostate cancer progression

“…The relationship between circulating and prostate tissue levels of androgens has been addressed in several studies (Bartsch et al 1986, Miyoshi et al 2014, Cook et al 2017, Neuzillet et al 2017. Overall, intraprostatic levels of DHT and testosterone, as well as dehydroepiandrosterone (DHEA) and androgen metabolites such as androstane-3β,17βdiol (3β-diol) are 5-to 10-fold higher in prostate tissue than those in the serum.…”