Effect of 16 beta-ethyl-17 beta-hydroxy-4-estren-3-one (TSAA-291) on the binding of promegestone (R5020) and methyltrienolone (R1881) to hyperplastic and neoplastic human prostate.
The effect of a synthetic steroidal compound TSAA-291 (16 beta-ethyl-17 beta-hydroxy-4-estren-3-one) on the binding of methyltrienolone (R1881) and promegestone (R5020) to hyperplastic and neoplastic human prostate was investigated. TSAA-291 inhibits both androgen and progestogen binding to hyperplastic and neoplastic human prostate. Glycerol density gradient analysis revealed that the inhibition of promegestone (R5020) binding by TSAA-291 was significantly greater than that of methyltrienolone (R1881) in both hyperplastic and neoplastic human prostate. The nature of the inhibition was competitive as determined by Scatchard analysis and double reciprocal plots. Comparison of the Ki values for the inhibition by TSAA-291 of R1881 binding (3.2 X 10(-7) M) and of R5020 binding (2.0 X 10(-8) M) suggests that TSAA-291 binds to progesterone receptor with a greater affinity than to androgen receptor. Our results suggest that the effectiveness of the drug in the treatment of benign hyperplasia might be due not only to its anti-androgenic properties but also due to its ability to inhibit progesterone receptor.
D001667:Binding, Competitive; D002499:Centrifugation, Density Gradient; D003534:Cyproterone / Q000031:analogs & derivatives / Q000378:metabolism; D017373:Cyproterone Acetate; D013196:Dihydrotestosterone / Q000378:metabolism; D004963:Estrenes / Q000378:metabolism*; D006801:Humans; D008297:Male; D008433:Mathematics; D015741:Metribolone; D009277:Nandrolone / Q000031:analogs & derivatives* / Q000494:pharmacology; D009649:Norpregnadienes / Q000378:metabolism*; D011397:Promegestone / Q000378:metabolism*; D011470:Prostatic Hyperplasia / Q000378:metabolism*
D004963:Estrenes; D009649:Norpregnadienes; D013196:Dihydrotestosterone; D015741:Metribolone; D017373:Cyproterone Acetate; D009277:Nandrolone; D011397:Promegestone; D003534:Cyproterone; C005671:oxendolone