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Antiandrogenic Effect of Spirolactones: Mechanism of Action

INSERM U-36 75005 Paris France

Abstract

Spirolactones are aldosterone antagonists which inhibit the binding of aldosteroneto the renal mineralocorticoid receptor. These molecules also possess an antiandrogenic effect which could be due, among other possibilities, to a peripheral antagonism of androgens. This hypothesis has been tested in the present study. From in vivo experiments, spironolactone and K( canrenoate appear to inhibit the binding of [³H]5dihydrotestosterone [³H]DHT to the cytosolic and nuclear receptor of the rat ventral prostate. The doses used are in the same range as those used for demonstrating the antimineralocorticoid effect of these molecules. In vitro incubations and in vitro displacement studies show that spironolactone and K canrenoate are respectively about 20 and 100 times lesseffective than DHT in displacing 50% of 5 x 10^-10 M [³H]DHTfrom its receptor. Spirolactones are also able to compete with [³H]DHT for the specific 8 S cytosolic receptor. Neither spironolactone nor K^x canrenoate decreases prostatic5-reductase activity, even at a concentration as high as 10^-5M. Itseems likely that spirolactones, besides their action on testosterone biosynthesis, exert theirantiandrogenic activity via a peripheral androgen antagonism. (Endocrinology 97: 52, 1975)

Received July 19, 1974.

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