Selective inhibition of the 5 alpha-reductase of the rat epididymis.
The effect of several synthetic steroids belonging either to the 4-aza-3-oxo-steroid family or to androstene and androstane derivatives was investigated "in vitro" on the epididymal as well as prostatic 5 alpha-reductase activity. For this purpose rat caput epididymis and prostate were incubated with the different steroidal compounds at molar concentrations of 10(-7), 10(-6), and 10(-5) in the presence of labelled testosterone as substrate. The steroids 4-MA (17 beta, N,N-diethyl-carbamoyl-4-aza-5 alpha-androstan-3-one) and 4-OH-A (4-hydroxy-androstenedione), already known to be effective 5 alpha-reductase inhibitors at the level of the prostate, have been used as reference molecules. The 5 alpha-reductase activity was evaluated by measuring pg of dihydrotestosterone (DHT) formed in 2 h of incubation by mg of tissue. The steroids A, B, C, F, G and I inhibit the formation of DHT in the rat epididymis although to different extents; they are also equally effective on the formation of DHT in the rat prostate. The steroids D, E, H and L are devoid of any inhibitory property on the formation of DHT in both the rat epididymis and prostate. The most interesting results were obtained with compound M which exhibits a dose-dependent and significant inhibitory effect on the formation of DHT in the epididymis, but it is inactive at the level of the prostate. These findings suggest that it is possible (a) to selectively interfere with the 5 alpha-reductase of the epididymis without affecting that present in the prostate, and (b) consequently to envisage new ways to regulate male fertility.
Zoppi
S
S
Department of Endocrinology, University of Milano, Italy.
Lechuga
M
M
Motta
M
M
D013741:3-Oxo-5-alpha-Steroid 4-Dehydrogenase / Q000378:metabolism; D058891:5-alpha Reductase Inhibitors; D000735:Androstenedione / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D001378:Azasteroids / Q000494:pharmacology; D013196:Dihydrotestosterone / Q000031:analogs & derivatives / Q000378:metabolism / Q000494:pharmacology; D004822:Epididymis / Q000201:enzymology*; D066298:In Vitro Techniques; D008297:Male; D015394:Molecular Structure; D011720:Pyrazoles / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D013256:Steroids / Q000494:pharmacology*
D058891:5-alpha Reductase Inhibitors; D001378:Azasteroids; D011720:Pyrazoles; D013256:Steroids; D013196:Dihydrotestosterone; D000735:Androstenedione; C031563:17-N,N-diethylcarbamoyl-4-methyl-4-azaandrostane-3-one; D013741:3-Oxo-5-alpha-Steroid 4-Dehydrogenase; C014594:formestane