Androgens and estrogens: their interaction with stroma and epithelium of human benign prostatic hyperplasia and normal prostate

Abstract

Growth and integrity of human prostatic epithelium is strongly dependent upon the adjacent stroma. Furthermore, the human prostate is under the control of sex hormones. Both facts prompted us to compare epithelium with stroma of human benign prostatic hyperplasia (BPH) and normal prostate (NPR) concerning their metabolism, binding and tissue concentrations of androgens and estrogens. In vitro metabolism was analyzed by t.l.c., androgen and estrogen binding sites were determined by a charcoal adsorption technique, androgen and estrogen tissue concentrations were measured by RIA. The main results are--(1) Metabolism: BPH stroma shows 2-3 times higher 5 alpha-reductase activity than epithelium. This high 5 alpha-reductase activity in BPH stroma dictates the differences between unseparated BPH and NPR, in the former the 5 alpha-reductase activity being 2 times higher. The 3 alpha(beta)-hydroxysteroid dehydrogenase (HSDH) activity is more evenly distributed between stroma and epithelium of BPH and NPR. The ratios of 5 alpha-reductase to HSDH activity in the various tissue fractions indicate that the highest enzymatically regulated 5 alpha-dihydrotestosterone (DHT) enrichment must occur in BPH stroma. (2) Tissue concentrations: unseparated BPH contains 2.2 times more DHT than NPR. About 70% of the total DHT content is found in nuclear fractions, whereby the nuclear DHT content of BPH stroma is significantly higher than that of BPH epithelium. In addition, nuclei of BPH stroma contain significantly more estradiol than epithelial nuclei. (3) Binding: the androgen receptor is evenly distributed between epithelium and stroma of BPH, while the estrogen receptor is preferably assayed in BPH stroma. These studies indicate that the BPH stroma is not only a preferential tissue for 5 alpha-reductase activity and DHT enrichment but also for nuclear estradiol accumulation.