T Cantor | PubMed Health

PubMed1976

Effect of megestrol acetate (Megace) on steroid metabolism and steroid-protein binding in the human prostate.

Megestrol acetate (Megace), an antiandrogen, was administered in a dosage of 80 mg daily to 6 patients with benign prostatic hypertrophy (BPH) for 4 to 25 days prior to transurethral resection of the prostate (TURP). Surgical tissue from drug-treated patients was compared to untreated controls in regard to: 1) the enzymatic reduction of testosterone (T) and dihydrotestosterone (DHT); 2) DHT binding to a cytosol receptor protein; 3) tissue levels of endogenous dihydrotestosterone and androstanediols (diols). When minced prostate was incubated with 3H-T and 14C-androstenedione for 1 h at 37 C, prostate 5alpha-reductase activity, measured as reduced products formed from substrate, decreased to 31% and 39%, respectively, of the control values. Prostate 3-oxido-reductase enzyme activity, measured as diols formed from 3H-DHT, was decreased to neglible values in Megace-treated patients compared to an 8.7% conversion to diols in controls. No 3H-DHT binding to a cytosol receptor protein could be demonstrated in 4 out of 5 prostates from Megace-treated patients, whereas the presence of such a receptor was noted in 14 out of 17 untreated controls. Endogenous DHT levels in Megace-treated patients averaged 1.1 ng/g (SE = 0.26), significantly less than the average of 3.9 ng/g (SE = 0.49) found in controls (P less than 0.001). No significant difference was noted in endogenous diols. In addition to these effects on tissue, Megace significantly decreased plasma levels of T, LH, and FSH at the end of the 4- to 25-day period; plasma prolactin levels did not change. Continued studies of Megace for the possible treatment of benign prostatic hypertrophy may be warranted since the drug appears to block several important biochemical steps which mediate the effects of androgen on the human prostate.

3-Oxo-5-alpha-Steroid 4-Dehydrogenase↗

PubMed1975

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.

Aged↗