Selective inhibition of the 5α-reductase of the rat epididymis

Abstract

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 5α-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 β, N, N-diethyl-carbamoyl-4-aza-5 α-androstan-3-one) and 4-OH-A (4-hydroxy-androstenedione), already known to be effective 5α-reductase inhibitors at the level of the prostate, have been used as reference molecules. The 5α-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 5α-reductase of the epididymis without affecting that present in the prostate, and (b) consequently to envisage new ways to regulate male fertility.