Effect of the in vivo treatment with the synthetic steroid 17 beta-methoxy-17-methyl-(5 alpha)-1 H'-androstane-(3,2-c) pyrazole (17MM) on the in vitro formation of DHT in the epididymis of the rat.
Adult male Sprague-Dawley rats were injected subcutaneously (s.c.) for 21 days either with the synthetic steroid 17 beta-methoxy-17-methyl-(5 alpha)-1 H'-androstane-(3,2-c) pyrazole (17MM) at two dose levels (0.1 and 1 mg/kg/day) or with the vehicle used to dilute the steroid. At autopsy, caput epididymes and ventral prostates were removed and incubated in vitro. The effect on the 5 alpha-reductase (5 alpha-R) activity was evaluated by measuring the amounts of DHT formed from 14C-testosterone (14C-T) used as the substrate. The in vivo administration of 17MM at the dose of 0.1 mg/kg/day resulted in a significant decrease in the formation of DHT at the level of the epididymis, while there was no effect on the prostate. The dose of 1 mg/kg/day did not induce any modification in the formation of DHT in either organ. The determination of serum LH showed that the treatment with either dose did not alter serum LH titers. These findings suggest that the in vivo treatment with 17MM lowers the in vitro formation of DHT from T at the epididymal, but not at the prostatic level and consequently suggests a selective inhibitory effect of 17MM on the 5 alpha-R present in the epididymis.
Zoppi
S
S
Department of Endocrinology, University of Milano, Italy.
Lechuga
M
M
Motta
M
M
D058891:5-alpha Reductase Inhibitors; D000731:Androstanes / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D013196:Dihydrotestosterone / Q000378:metabolism*; D004822:Epididymis / Q000187:drug effects* / Q000378:metabolism*; D066298:In Vitro Techniques; D007279:Injections, Subcutaneous; D007986:Luteinizing Hormone / Q000097:blood; D008297:Male; D009928:Organ Specificity; D011467:Prostate / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley
D058891:5-alpha Reductase Inhibitors; D000731:Androstanes; D013196:Dihydrotestosterone; D007986:Luteinizing Hormone