Interaction of Spironolactone and Digitalis with the 5α Dihydrotestosterone (DHT)1Receptor of Rat Ventral Prostate1

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Abstract
The aldosterone antagonist, spironolactone, blocks the effects of exogenously administered androgen in rat. Interaction of the drug with androgen at the target tissues may occur. The possible interaction of spironolactone with 5.alpha.-dihydrotestosterone (DHT) receptor of rat ventral prostate was studied. The competitive receptor assay used involves precipitation of the 105,000 .times. g supernatant of the homogenized tissue with protamine sulfate, removal of the unprecipitated cytosol and incubation of the precipitate in the presence of the appropriate [3H]DHT steroid solution at 0.degree. C for 18 h. Using this method the Kd(dissociation constant) for DHT in the rat prostate was in the range of 1.9-4.0 .times. 10-9 M and the binding capacity was 0.21 pmol/mg protein. Spironolactone interfered with the binding of DHT to the precipitated cytosol and displayed an estimated Kd of 1.3-4.6 .times. 10-8 M. Several digitalis preparations were similarly studied. Digitoxin and digitoxigenin also interfered with the binding of [3H]DHT and had an estimated Kd of 0.8-3.6 .times. 10-8 M. Digoxin interacted less strongly and its estimated Kd was 10-6 M. An interaction spironolactone and digitalis with the DHT receptor is suggested and may help explain some of their antiandrogenic actions in the rat and in man.

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