Androgen Receptors

Abstract In rat ventral prostate there are at least two soluble cytoplasmic proteins which specifically bind 3H-5α-dihydrotestosterone (3H-17β-hydroxy-5α-androstan-3-one). Only one of the 3H-5α-dihydrotestosterone-protein complexes (Complex II) can be retained by cell nuclei of the same tissue. The other 5α-dihydrotestosterone-binding protein (Complex I) can be separated from Complex II by an ammonium sulfate fractionation and a Sephadex gel filtration. Complex I preparations strongly inhibit the retention of Complex II by the prostate cell nuclei. The extent of the retention of prostate Complex II by cell nuclei of other rat tissues (liver, brain, thymus, and diaphragm), which are less sensitive to androgen, is relatively small. The cytosol fraction of liver contains very little of the protein which can form a complex (with 5α-dihydrotestosterone) retainable by cell nuclei of rat liver or ventral prostate. Cell nuclei of rat ventral prostate appear to contain specific nuclear acceptors which can selectively retain the 5α-dihydrotestosterone-receptor protein Complex II. The ability of cell nuclei to retain Complex II is rapidly lost when the nuclei are heated for 10 min at temperatures higher than 50°. Complex II is even less stable to heating. At 37° about one-half of the bound 5α-dihydrotestosterone is released from Complex II in 10 min. Complex II, by itself, is not retained firmly by prostate cell nuclei in the absence of 5α-dihydrotestosterone. This suggests that 5α-dihydrotestosterone binds to the receptor protein in such a way that the complex formed will have the structural requirement to fit the binding site of the prostate nuclear acceptor. Other steroids such as 5β-dihydrotestosterone, testosterone, 5α-androstane-3, 17-dione, 3α (or 3β),-17β-dihydroxy-5α-androstane, 4-androstene-3, 17-dione, 17β-estradiol, cortisol, and progesterone are not effective for this purpose. The steroid- and tissue-specificity of the cell-free systems strongly suggests that 5α-dihydrotestosterone plays a central role in the retention of an androgen receptor protein by prostate nuclei in vivo. The biological importance of the process is also underlined by the fact that cyproterone (6-chloro-17α-hydroxy-1,2α-methylene-4,6-pregnadiene-3,20-dione) 17α-acetate, a potent antiandrogen, also inhibits the retention process in the cell-free system.