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.
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.
D000726:Androgen Antagonists / Q000008:administration & dosage / Q000494:pharmacology; D000818:Animals; D002369:Castration; D002467:Cell Nucleus / Q000378:metabolism; D002499:Centrifugation, Density Gradient; D002850:Chromatography, Gel; D003534:Cyproterone / Q000494:pharmacology; D003600:Cytosol / Q000378:metabolism; D013196:Dihydrotestosterone / Q000378:metabolism; D007273:Injections, Intramuscular; D046911:Macromolecular Substances; D008297:Male; D009277:Nandrolone / Q000031:analogs & derivatives* / Q000494:pharmacology; D011467:Prostate / Q000378:metabolism*; D051381:Rats; D011944:Receptors, Androgen / Q000096:biosynthesis*; D011987:Receptors, Steroid / Q000096:biosynthesis*; D013739:Testosterone / Q000378:metabolism*
D000726:Androgen Antagonists; D046911:Macromolecular Substances; D011944:Receptors, Androgen; D011987:Receptors, Steroid; D013196:Dihydrotestosterone; D013739:Testosterone; D009277:Nandrolone; D003534:Cyproterone