Receptors and binding of androgens in the prostate

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The interaction between androgens and prostatic and other androgen-dependent tissues has been investigated in castrated male rats in vivo following administration of [1,2- 3H] testosterone of high specific activity. Radioactive androgens were concentrated and retained in such tissues for a number of hours. The receptors in the ventral prostate appeared to have a limited capacity, as administration of 20 μg non-radioactive testosterone simultaneously with the tritiated testosterone significantly reduced the uptake of radioactivity, and 500 μg completely abolished it. Synthetic androgens, antiandrogens, progesterone and corticosterone also reduced the uptake. Autoradiography of the prostatic tissue revealed a selective labelling of the glandular epithelium, with most of the radioactivity associated with the nuclei. This conclusion was supported by subcellular fractionation of homogenized prostatic tissue. Isolation and identification of the radioactive steroids confirmed previous observations that 5α-dihydrotestosterone was the quantitatively most important radioactive compound in the various accessory sex organs. 5α-dihydrotestosterone accounted for 50–72 per cent of the radioactivity, whereas 3–17 per cent was recovered as unchanged testosterone. Following the administration of [1,2- 3H]-androstenedione, accumulation of radioactivity was also observed in androgen-dependent tissues, and about 50 per cent of the radioactivity was identified as 5α-dihydrotestosterone. By Sephadex ® G-100 gel filtration of a 105.000 g supernatant of a homogenate of the ventral prostate obtained one or two hours after the administration of [1,2- 3H]-testosterone, the major fraction of the radioactivity was associated with macromolecules excluded from the gel. The radioactivity bound to the macromolecules was extractable with ether, suggesting a non-covalent binding, and 5α-dihydrotestosterone accounted for more than 90 per cent of the radioactivity. This cytosol androgen-macromolecule complex was destroyed by proteolytic enzymes and SH-reagents, but was unaffected by RNase and DNase. Incubations with [1,2- 3H]-5α-dihydrotestosterone and a 105.000 g supernatant of the ventral prostate suggested the existence of two different species of cytosol macromolecules with binding affinity for 5α-dihydrotestosterone, one of which was excluded from the gel during Sephadex ® G-100 gel chromatography, whereas the other was slightly retained. In the experiments with [1,2- 3H]-testosterone administration in vivo the radioactive 5α-dihydrotestosterone was mostly bound to the former. Attempts to isolate [ 3H]-5α-dihydrotestosterone in muscle tissue following [1,2- 3H]-testosterone administration were unsuccessful, suggesting that 5α-dihydrotestosterone may not be involved in the action of androgens on such tissue.