A systematic study of testosterone metabolism in benign prostatic hypertrophy (BPH): in vitro results.
An in vitro system for testing steroids which might be effective in treating benign prostatic hypertrophy (BPH) has been developed based upon the transformation of H-3-testosterone into the 5-alpha-reduction products dihydrotestosterone and 3-alpha-androstanediol. In scrutinizing the influence of the amount of BPH-tissue, time, and pH, 300 mg of tissue incubated for 2 h at the physiological pH of 7.4 were used in the standard experiment. -The H-3-testosterone concentration was varied from 0.17-100 times 10-8 M. Plotting the resulting 5-alpha-reduction products as a function of testosterone concentration a hyperbolic pattern of enzyme kinetics ensued. Performing a double reciprocal plot of 4 experiments with double determination of each value regression lines could be computed. Those two regression lines most different in their slopes were considered "normal" limits. The rate of H-3-testosterone metabolism could not be enhanced after the endogenous testosterone content within the prostate glands had been used up by means of a preincubation. Scrutinizing the effect of heparin, a weak non-specific enzyme inhibitor, no suppression of the appearance of 5-alpha-reduction products was found. Damaging the BPH-cells, however, by repetitive freezing and thawing lead to an almost complete inhibition of H-3-testosterone turnover.
D015113:Androstane-3,17-diol / Q000032:analysis; D000731:Androstanes / Q000032:analysis; D000735:Androstenedione / Q000032:analysis; D046508:Culture Techniques; D013196:Dihydrotestosterone / Q000032:analysis; D005615:Freezing; D006493:Heparin / Q000494:pharmacology; D006651:Histocytochemistry / Q000379:methods; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007700:Kinetics; D008297:Male; D011470:Prostatic Hyperplasia / Q000378:metabolism*; D013739:Testosterone / Q000378:metabolism*; D013997:Time Factors; D014316:Tritium
D000731:Androstanes; D013196:Dihydrotestosterone; D014316:Tritium; D015113:Androstane-3,17-diol; D013739:Testosterone; D000735:Androstenedione; D006493:Heparin