Interaction of Digitalis and Spironolactone with Human Sex Steroid Receptors

Abstract

Spironolactone and digitoxin have previously been shown to interact with cytosol androgen and estrogen receptors, respectively, in the rat. The interaction of digitoxin with human uterine cytosol estrogen binding protein and spironolactone with human prostate and newborn prepuce cytosol dihydrotestosterone (DHT) binding protein has been analyzed in this study. Specific estradiol binding was found only in premenopausal uteri. The dissociation constant for estradiol binding was 0.6–2.3 × 10^–9 M (n = 12). Digitoxin in concentrations varying between 0.5–2.0 × 10^–6 M inhibited specific estradiol binding with a Ki of 2.0–7.3 × 10^–7 M (n = 9). The dissociation constants for DHT and the human androgen cytosol binding protein in prostate and newborn prepuce were 0.27–3.0 × 10^–8 M (n = 12) and 0.6–2.0 × 10^–8 M (n = 5), respectively. Spironolactone at concentrations of 0.3–2.0 × 10^–6 M competitively inhibited this binding with an affinity about one order of magnitude less than that of DHT. Digitoxin and spironolactone did not displace estradiol and DHT, respectively, from testosterone-estrogen binding globulin in male or female plasma. The interaction of digitoxin with the human uterus estrogen binding protein and spironolactone with the human prostate and prepuce androgen binding protein is similar to our previous observations in the rat, and may explain the weak estrogenic effects of digitoxin and spironolactone in man. (J Clin Endocrinol Metab46: 338,1977)