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  • Title: Anti-androgen TSAA-291. V. Effects of the anti-androgen TSAA-291 on the androgen-receptor complex formation from [3H]testosterone in rat ventral prostates.
    Author: Sudo K, Yoshida K, Kimura Y, Nakayama R.
    Journal: Acta Endocrinol Suppl (Copenh); 1979; 229():67-81. PubMed ID: 294108.
    Abstract:
    Intramuscular administration of a new steroidal anti-androgen, TSAA-291 (16 beta-ethyl-17 beta-hydroxy-4-oestren-3-one), in doses of 0.05, 0.5 and 5 mg/kg body weight reduced the in vivo uptake of [3H]testosterone by the ventral prostate of castrated rats of 78, 59 and 37% of the control level, respectively. Analysis on subcellular fractions of the prostate by gel-filtration and sucrose density-gradient centrifugation followed by thin layer chromatographic identification of testosterone metabolites revealed that 5 alpha-dihydrotestosterone (5 alpha-DHT) which was found to be largely bound to macromolecules in the cytosol and nucleus was the predominant metabolite even in the presence of the anti-androgen, and radioactivities corresponding to the 5 alpha-DHT-macromolecular complexes were decreased by the anti-androgen. TSAA-291 also inhibited the in vitro formation of the 5 alpha-DHT-macromolecular complexes in both cytosol and nucleus from minced prostates incubated with [3H]testosterone. The importance of the findings is discussed in connection with the mode of anti-androgenic action of TSAA-291 in terms of the interaction with the androgen receptor.
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