A protein factor that can inhibit binding of the androgen-receptor complex to the nuclear chromatin has been isolated from the cytosol of the ventral prostate of rats. The inhibition is reversible and not caused by an irreversible destruction of the receptor or the chromatin. The inhibitor also can promote, by a temperature-dependent rocess, the release of steroid-receptor complex already boundto chromatin. It is conceivable that such a protein factor plays a regulatory role in the nuclear-cytoplasmic recycling or chromatin binding of the steroid hormone receptor.Inside the target cells, steroid hormones can bind to specific high-affinity and low-capacity receptor proteins. The steroid-receptor complexes can then interact with the nuclear chromatin acceptor sites. Such a process is believed to be essential for steroid hormones to elicit a majority of cellular responses (1-4). If this view is correct, it is very important to explore the possibility that the target cells may have an inherent mechanism that regulates the interaction of the steroid-receptor complex with the genomic machinery and thereby controls the hormonal responses.In 1971, we reported that the rat ventral prostate, a target tissue of androgens, has a cytosol protein that can interfere with the association of the prostate androgen-receptor complex with the cell nuclei or chromatin (5). In the last several years, other investigators also reported the existence of similar inhibitors in the cytosol of rat uterus (6), chick oviduct (7), rat liver (8), and rat hepatoma cells (9). Because bovine serum albumin also exhibits inhibitory activities in some of these experimental systems (6, 7), such an inhibition has not been considered to be a highly specific phenomenon.We have purified the inhibitor from the rat ventral prostate, and the experimental evidence presented here indicates that this prostate inhibitor is a specific protein capable of preventing the androgen-receptor complex from binding to the nuclear acceptor site (5, 10) and also of promoting the release of the complex from the chromatin.EXPERIMENTAL PROCEDURES Cellular Preparations. Sprague-Dawley male rats (300400 g) were used in this study. They were killed 20 hr after castration. The radioactive androgen-receptor complex was prepared by a modification of the method described previously (5). Ventral prostates were minced, homogenized, and centrifuged at 10,000 X g for 10 min. The supernatant fraction was incubated with 0.5 nM 5a-dihydro[1,2-3H]testosterone (40 Ci/ mmol, unless noted otherwise) for 1 hr. The incubation mixture was centrifuged at 100,000 X g for 1 hr. The cytosol fractionThe publication costs of this article were defrayed in part by page charge payment. This article must therefore be hereby marked "advertisement" in accordance with 18 U. S. C. §1734 solely to indicate this fact. 5969 was brought to 40% saturation with respect to ammonium sulfate to precipitate the specific 5a-dihydro[3H]testosteronereceptor complex. The complex was suspended in 20 mM Tris-HCl at pH 7...
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