Effect of diethylstilbestrol diphosphate on activity of 5 alpha-reductase in human prostate.
Following the intravenous drip infusion of diethylstilbestrol diphosphate (DES-DP), the diethylstilbestrol (DES) concentrations both in plasma and prostatic tissue obtained from patients with prostatic carcinoma were measured by radioimmunoassay and the effects of DES on the activity of 5 alpha-reductase in the prostate obtained from BPH patients were determined in vitro. Further, the changes in the activity of 5 alpha-reductase in the prostate from the BPH patients who received DES-DP infusion were also determined. The plasma and prostatic tissue concentrations of DES rapidly declined from 2.3 micrograms/ml and 1.6 micrograms/g wet weight 1 h after DES-DP infusion to 0.8 microgram/ml and 0.25 microgram/g wet weight 3 h after DES-DP infusion, respectively, and decreased gradually thereafter until 24 h. In in vitro study progressed by BPH specimens, the 5 alpha-reduction rate was completely inhibited by an addition of 5 x 10(-4) M of DES and the DES concentration on the inhibition rate of 50% was 4 x 10(-5) M. In in vivo study, the mean production rate of 5 alpha-dihydrotestosterone (DHT) in the control specimens of BPH without infusion of DES-DP was 14.0 +/- 3.4 nmol/15 min/mg protein and the production rate of DHT in the DES-DP infused specimens of BPH was 14.7 nmol/15 min/mg protein at 3 h and 15.2 nmol/15 min/mg protein at 12 h after the termination of DES-DP infusion. These results indicated that intravenously administered DES-DP did not act via the inhibition of 5 alpha-reductase in the prostatic cells for producing the clinical effects.
Usui
T
T
Department of Urology, Shimane Medical University, Izumo, Japan.
Ishibe
T
T
Nakamura
K
K
Mizutani
M
M
Yasukawa
A
A
D013741:3-Oxo-5-alpha-Steroid 4-Dehydrogenase / Q000032:analysis / Q000378:metabolism*; D004054:Diethylstilbestrol / Q000031:analogs & derivatives* / Q000032:analysis / Q000097:blood / Q000494:pharmacology; D013196:Dihydrotestosterone / Q000378:metabolism; D006801:Humans; D008297:Male; D011467:Prostate / Q000032:analysis / Q000201:enzymology*; D011470:Prostatic Hyperplasia / Q000201:enzymology*; D011471:Prostatic Neoplasms / Q000378:metabolism*; D013997:Time Factors
D013196:Dihydrotestosterone; D004054:Diethylstilbestrol; C004955:fosfestrol; D013741:3-Oxo-5-alpha-Steroid 4-Dehydrogenase