Effect of 1,4,6-Androstatriene-3,17-Dione (ATD), 4-Hydroxy-4-Androstene-3,17-Dione (4-OH-A) and 4-Acetoxy-4-Androstene-3, 17-Dione (4-Ac-A) on the 5α-reduction of androgens in the rat prostate

Abstract

The present study reports the effects exerted by 1,4,6-androstatriene-3,17-dione (ATD), 4-hydroxy-4-androstene-3,17-dione (4-OH-A) and 4-acetoxy-4-androstene-3,17-dione (4-Ac-A), three steroids known to inhibit the aromatization of androgens to estrogens, on the in vitro metabolism of labelled testosterone (T), dihydrotestosterone (DHT) and androstenedione (delta-4-A) in the ventral prostate of adult male rats. It has been found that ATD, in the concentration tested, does not influence the conversion of labelled T into DHT, but decreases the formation of 5α-androstane-3α,17β-diol and 5α-androstane-3β,17β-diol (diols). On the contrary, 4-OH-A and 4-Ac-A simultaneously decrease the formation of DHT and the diols. When T is used as the substrate, the presence in the medium of these three steroids enhances the formation of delta-4-A and of 5α-androstanedione (5α-A). ATD, but not 4-OH-A and 4-Ac-A inhibits the conversion of labelled DHT into the diols. The transformation of labelled delta-4-A into 5α-A is not modified by either ATD or 4-OH-A, while 4-Ac-A exerts only a small inhibition. These results suggest that the three aromatase inhibitors tested are able to profoundly modify the metabolism of T in the ventral prostate of the rat. In particular: (1) 4-OH-A and 4-Ac-A are able to inhibit the conversion of T into DHT; (2) ATD is able to inhibit the conversion of DHT into the diols; (3) ATD and 4-OH-A do not inhibit the process of 5α-reduction of delta-4-A into 5α-A, while 4-Ac-A exerts only a minor effect. It is suggested that in the ventral prostate of the rat there are two different 5α-reductase isoenzymes, one sensitive to the inhibitory effect of the steroid tested and which is responsible for the conversion of T into the 5α-reduced metabolites of the 17-OH series (DHT and the diols), and a second one, insensitive to the effects of the three steroids, which affects the conversion of delta-4-A into 5α-A.