Studies on the possible existence of two 5 alpha-reductases in the rat prostate

In the first group of experiments, the in vitro metabolism of labelled testosterone has been studied in the ventral prostate of young (2 months) and old (15 and 22 months) male rats. It has been found that the prostate of 2-month-old animals converts testosterone into dihydrotestosterone (5 alpha-androstane-17 beta-ol-3 one, DHT) and into the diols (5 alpha-androstane-3 alpha-17 beta-diol and 5 alpha-androstane-3 beta,17 beta-diol) with considerable yields. The prostate of young animals is also able to convert testosterone into delta 4-androstenedione (delta 4-A), 5 alpha-androstanedione (5 alpha-A) and androsterone (A); however, the amounts of these metabolites are lower than those of DHT and the diols. It has been found that ageing induces major alterations in the prostatic metabolism of testosterone. In particular, a progressive and significant decrease in the formation of DHT and of the diols has been found in animals of 15 and 22 months of age. Advancing age induces, on the contrary, an increase of the formation of delta 4-A and of the 5 alpha-reduced metabolites of the 17-keto series (5 alpha-A + A). In the second group of experiments, the effects exerted by 4-hydroxy-4-androstene-3,17-dione (4-OH-A) on the in vitro metabolism of labelled testosterone and delta 4-A in the ventral prostate of adult male rats have been studied. It has been found that 4-OH-A, when added to the incubation media, decreases the formation of DHT and of the diols, when labelled testosterone is used as the substrate. The presence in the media of this steroid enhances the formation of delta 4-A and of 5 alpha-A. The transformation of labelled delta 4-A into 5 alpha-A is not modified by the presence in the medium of 4-OH-A. From the two groups of experiments, it is concluded that in the ventral prostate of the rat there are two different 5 alpha-reductase isoenzymes, one sensitive to age and to the inhibitory effect of 4-OH-A (and which is responsible for the conversion of testosterone into the 5 alpha-reduced metabolites of the 17-OH series, DHT and the diols), and a second one, insensitive to age and to the effects of 4-OH-A, which affects the conversion of delta 4-A into 5 alpha-A.