Evidence for a specific dihydrotestosterone-binding cytosol receptor in the human prostate.
A technique for the demonstration of a human steroid and organ-specific prostate cytosol receptor is described. Tissue from 17 patients with benign prostatic hypertrophy was incubated in Eagle's medium with 3H-testosterone (T) .06 nM following pre-incubation with an anti-androgen. The minces were homogenized and the cytosol fraction obtained. The cytosol was then fractionated on a duo-gel column of G-50 Sephadex over Bio-gel A 1.5m and fractions counted for 3H, assayed for protein and plotted graphically. Three main peaks were seen. Only the second peak (approximately 150,000 mol wt), which contained predominantly dihydrotestosterone (DHT), was significantly and reproducibly inhibited by 2.1 muM cyproterone acetate (Cyp A) pre-incubation. This inhibiton was considered a specific indicator for receptor since Cyp A at muM had little effect (less than 10%) on 3H-DHT binding to plasma. Similar results were noted for other anti-androgens tested, but cortisol and etiocholanolone had no effects on 3H-5alpha DHT binding to prostate cytosol. Steroid-protein peaks for fractionated human thyroid, muscle, and spleen cytosol were not inhibited by Cyp A. Fractionated kidney cytosol contained a 3H-T-binding protein peak which was significantly decreased by Cyp A. Pronase incubation and heating at 50 C for 30 min both resulted in either a significant decrease or complete loss of receptor. Gel filtration analysis of 3H-cytosol derived from human prostate minces pre-incubated with and without Cyp A, provides a relatively rapid technique for the demonstration of cytosol receptor in approximately 80% of prostates from patients with benign prostatic hypertrophy.
D000368:Aged; D003534:Cyproterone / Q000494:pharmacology; D003600:Cytosol / Q000378:metabolism*; D013196:Dihydrotestosterone / Q000378:metabolism*; D005043:Etiocholanolone / Q000494:pharmacology; D006801:Humans; D006854:Hydrocortisone / Q000494:pharmacology; D066298:In Vitro Techniques; D008297:Male; D008875:Middle Aged; D009928:Organ Specificity; D011467:Prostate / Q000378:metabolism*; D011470:Prostatic Hyperplasia / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000187:drug effects
D011956:Receptors, Cell Surface; D013196:Dihydrotestosterone; D005043:Etiocholanolone; D003534:Cyproterone; D006854:Hydrocortisone