Relative binding affinity at metribolone androgenic binding sites of various antiandrogenic agents

Sebaceous glands are androgen sensitive structures with activity reduced by antiandrogens. We characterized the relative binding affinity of cyproterone acetate, 17 alpha-propyl-mesterolone, spironolactone (canrenoic acid), ethisterone and dexamethasone by means of the competitive binding analysis at metribolone (R1881) androgen binding sites. Using the DCC-assay (dextran-coated charcoal absorption) with the Scatchard plot and saturation analysis we quantified R1881 androgen binding sites from sebaceous glands situated in the ventral side of the pinna of the Syrian hamster. As parameters for ligand affinity at these binding sites served the ligand concentration for 50% displacement of 3H-labelled synthetic steroid R1881 in constant concentrations. The in vitro measurements of the used steroids were compared to the biologic sebosuppressive effect in vivo. 17 alpha-Propylmesterolone showed the highest affinity at the androgenic binding site followed by ethisterone, cyproterone acetate and spironolactone. The results, however, do not admit an interpretation about the mode of action of the given substances, which display their biologic activity either after systemic or topic administration. In vivo distribution problems and metabolizing procedures might be due to this discrepancy.