Biochemical characterization of prostatic nuclei. I. Androgen-induced changes in nuclear proteins

1. The fractional recovery of rat prostatic nuclei isolated by centrifugation differed markedly at various phases of androgen-induced growth. Nuclei obtained from prostate glands that had been under the influence of androgen (either endogenous or exogenous), were obtained in much lower yield in comparison to nuclei isolated from animals that had been deprived of androgen by castration. These differences in the facility of isolation of nuclei were abolished either by removing the outer membranes of the nuclei by treatment with Triton X-100 or by appropriate changes in the Mg²⁺ concentration of the isolation medium. 2. The volumes of the nuclei of prostatic epithelial cells obtained from glands in various states of testosterone-induced growth differ markedly. Similar observations were made with the isolated nuclei. The lowest nuclear volumes were observed in the prostates of castrated animals and these changes could be reversed by androgen therapy. 3. The ratio of the total amount of nuclear protein to the amount of DNA decreased following castration, and could be restored by 3 days of androgen therapy. When the nuclear proteins were fractioned into groups, the ratios of the isolated soluble (S₁), histone (H), and acidic (A) proteins to the amounts of DNA correlated with the overall changes in the total nuclear protein to DNA ratios. In contrast, the ratios of membrane (M) and soluble (S₂) proteins were not significantly altered during the entire course of androgen deprival and treatment. 4. Resolution of various classes of nuclear proteins by disc-gel electrophoresis, revealed that the patterns of the soluble proteins changed markedly following castration and were restored to normal patterns following testosterone administration. In addition, the very lysine-rich histone (F₁), decreased appreciably following castration but was restored to control levels by testosterone administration. Several of the nuclear membrane proteins appeared also to be altered both quantitatively and qualitatively by androgen treatment. In contrast, while the total amount of acidic and residual nuclear proteins decreased with castration, there was nevertheless only minimal qualitative changes in their electrophoretic patterns.