Formation, nuclear incorporation and enzymatic decomposition of androgen-receptor complex of rat prostate

Specific affinity of the prostate cytosol receptor for 5α-dihydrotestosterone was demonstrated by competitive experiment between testosterone and 5α-dihydrotestosterone. The binding of [1,2- 3H]-5α-dihydrotestosterone to the cytosol receptor of rat ventral prostate was not affected by simultaneous administration of nonradioactive testosterone, whereas the binding of [1,2- 3H]-testosterone to the receptor was severely suppressed by non-radioactive 5α-dihydrotestosterone. Binding capacity of the cytosol receptor for the tritiated 5α-dihydrotestosterone and testosterone was somewhat greater at 37°C than 4°C. The involvement of the cytosol receptor in retention of 5α-dihydrotestosterone by the nuclei of rat prostate was confirmed at 4° and 37°C. A 3α-hydroxysteroid dehydrogenase fraction which contained no 9S receptor was prepared from the prostate cytosol by precipitation with ammonium sulphate at 60–100% saturation. When [ 3H]-labeled 5α-dihydrotestosterone bound to the cytosol receptor (9S) was incubated with the 3α-hydroxysteroid dehydrogenase fraction in the presence of NADPH, a remarkable dissociation of the radioactivity from the receptor complex was observed. According to the analysis of the liberated steroids, the major radioactive steroid was identified as 5α-androstane-3α, 17β-diol, which bound to the receptor to a very limited extent. On the contrary, the remaining radioactivity bound to the receptor after incubation was principally due to 5α-dihydrotestosterone. The degradation of the androgen-receptor complex by the 3α-hydroxysteroid dehydrogenase in the cytosol suggests a possible process of intracellular decomposition of the complex, in relation to excretion of the steroid metabolite from the prostatic cells.