Stroma of human benign prostatic hyperplasia: preferential tissue for androgen metabolism and oestrogen binding

Abstract

Because of the well known stromal-epithelial interaction of various urogenital organs, it was of interest to compare quantitatively steroid metabolism and binding in epithelium (E) and stroma (S) of the human benign prostatic hyperplasia (BPH). Testosterone 5.alpha.-reductase activity was determined by TLC and androgen as well as estrogen binding sites by a charcoal adsorption technique after a steroid incubation period of 18 h at 0.degree. C, using methyltrienolone (R1881) and estradiol-17.beta. as tritiated ligands and unlabled R1881 and diethylstilbestrol as the respective competitors. The main results were as follows: using biochemical markers (acid phosphatase, hydroxyproline), an average 17% contamination of E by S and 6% of S by E was found; the molar optimum of NADPH for the enzyme reaction was nearly identical in E and S, ranging between 1 and 0.1 mM; the apparent Km of 5.alpha.-reductase was identical in both fractions, the mean being 0.15 .mu.M; the maximal rate of 5.alpha.-reductase activity (pmol 5.alpha.-reduced metabolites .cntdot. mg protein-1 .cntdot. 1 h-1) was 161 .+-. 28 (SEM [standard error of the mean]; n = 20), 66 .+-. 4.6 and 148 .+-. 6.6 in S, E and whole tissue fraction of BPH, respectively. In 2 normal prostates the means were: 88, 53 and 73, respectively; the androgen binding sites were evenly distributed between the cytosol of E and S, while measurable estrogen binding sites were found in 42% of the analyzed S but only in 5% of analyzed E. The 2.4 times higher 5.alpha.-reductase activity in S compared to E of the BPH is responsible for the .apprx. 2-2.5 times higher activity in the whole tissue fraction of BPH if compared with the normal prostate. Due to preliminary binding studies, estrogens might play an important role in the S fraction of BPH.