Assignment of anabolic-androgenic and antiandrogenic properties to some chlorine-substituted steroids on the basis of their binding characteristics to the androgen receptor of the rat seminal vesicle.
In this study we investigated the affinity of several 4-chlorinated and 1-ene derivatives of 17 alpha-methyltestosterone (MT) and 17 alpha-methyl-5 alpha-dihydrotestosterone (MDHT) to the androgen receptor, and, additionally, the effect of a few MT-derived steroids on the activity of the 5 alpha-reductase enzyme present in the rat seminal vesicle. From our results we conclude, that delta 1 or/and delta 4 double bonds in ring A counteract the inhibition of receptor-binding caused by chlorine-substitution at C4; the dissociation of myotropic and androgenic effects [= M/A dissociation] of 4-chloro-MT (as compared to MT) is due to its inactivation by 5 alpha-reductase in androgen target organs and/or to the inhibition of the conversion of endogenous testosterone to DHT; the M/A dissociation of 1-ene-MT and 4-chloro-1-ene-MT may be explained by their inability to be activated by 5 alpha-reductase; for the same reason, M/A dissociation can be assigned to the effects of 4 alpha-chloro-1-ene-DHT. We determined the short-term and long-term competition of cyproterone acetate and chlormadinone acetate with [3H]DHT for receptor binding at 0 degrees C and showed, that the complexes formed by these antiandrogens with the androgen receptor have equally reduced stabilities compared to the DHT-receptor complex.
D045930:Anabolic Agents / Q000378:metabolism*; D000726:Androgen Antagonists / Q000378:metabolism*; D000818:Animals; D001667:Binding, Competitive; D002713:Chlorine; D042944:Cholestenone 5 alpha-Reductase; D013196:Dihydrotestosterone / Q000031:analogs & derivatives* / Q000378:metabolism; D066298:In Vitro Techniques; D008297:Male; D008710:Methenolone / Q000378:metabolism; D008777:Methyltestosterone / Q000378:metabolism; D010088:Oxidoreductases / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D011944:Receptors, Androgen / Q000378:metabolism; D012669:Seminal Vesicles / Q000378:metabolism; D013256:Steroids / Q000145:classification / Q000378:metabolism*; D013329:Structure-Activity Relationship; D045165:Testosterone Congeners / Q000378:metabolism*
D045930:Anabolic Agents; D000726:Androgen Antagonists; D011944:Receptors, Androgen; D013256:Steroids; D045165:Testosterone Congeners; D013196:Dihydrotestosterone; D002713:Chlorine; D008710:Methenolone; D010088:Oxidoreductases; D042944:Cholestenone 5 alpha-Reductase; C008376:mestanolone; D008777:Methyltestosterone