title: Comparative effects and mechanisms of castration, estrogen anti-androgen, and anti-estrogen-induced regression of accessory sex organ epithelium and muscle.
abstract: We examined the effects and mechanisms of action of various endocrine manipulations on the epithelium and muscle preparations of the guinea pig seminal vesicle. Castration, which reduced the plasma testosterone level to 10 percent of normal, caused approximately 80 per cent reductions in epithelium wet weight and RNA and DNA contents. Estradiol benzoate effected similar reductions in plasma androgen and epithelial cell function in intact males. Reduction in plasma androgen level accounted for the estrogen-induced epithelial regression; no antiandrogenic effect of estrogen on the epithelium was detectable. All anti-androgens tested, flutamide, spironolactone, and cyproterone acetate, reduced epithelium weight in intact animals. Studies of the mechanism of cyproterone acetate action indicated its effects were attributable solely to an anti-androgenic action on the epithelium. The anti-estrogens, tamoxifen and nafoxidine, had no effect on the epithelium of intact animals when tested alone or in combination with cyproterone acetate. Regression of seminal vesicle muscle occurred only after castration or treatment of intact animals with cyproterone acetate. The action of cyproterone acetate on the muscle was attributable to blockade of the androgenic stimulus. The drug had no effect on plasma testosterone or estradiol levels and had no anti-estrogenic activity. In intact males estradiol reduced plasma testosterone to castrate levels, but did not alter muscle weight and nucleic acid levels. The potential deleterious effects of reduced plasma testosterone on the muscle were surmounted by direct estrogenic stimulation of the tissue. The anti-androgens, flutamide and spironolactone, and the anti-estrogens, tamoxifen and nafoxidine, had no effect on the muscle of intact males. Inasmuch as the regressive effects of castration on the epithelium and muscle can be duplicated in intact animals only by treatment with cyproterone acetate, this particular drug may provide the most effective nonsurgical treatment of prostatic neoplasia.
mesh_terms: D000726:Androgen Antagonists / Q000494:pharmacology*; D000818:Animals; D002369:Castration; D003534:Cyproterone / Q000494:pharmacology / Q000627:therapeutic use; D013196:Dihydrotestosterone / Q000494:pharmacology; D004848:Epithelium / Q000187:drug effects / Q000502:physiology; D004958:Estradiol / Q000494:pharmacology*; D004965:Estrogen Antagonists / Q000494:pharmacology*; D006168:Guinea Pigs; D008297:Male; D009132:Muscles / Q000187:drug effects / Q000502:physiology; D011471:Prostatic Neoplasms / Q000188:drug therapy; D012669:Seminal Vesicles / Q000187:drug effects* / Q000502:physiology
chemical_list: D000726:Androgen Antagonists; D004965:Estrogen Antagonists; D013196:Dihydrotestosterone; D004958:Estradiol; D003534:Cyproterone