Amplification of the Action of Aldosterone by 5α-Dihydrocortisol*

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Abstract
Elevated conversion rates of cortisol to 5.alpha.-dihydrocortisol (5.alpha.-DHF) were in a child with hypoaldosteronism, Na+ retention, hypokalemic alkalosis and hypertension. Studies investigating possible etiological roles for 5.alpha.-DHF in the rat urinary electrolyte bioassay in vivo show that 5.alpha.-DHF (30-100 .mu.g/100 g) had minimal mineralocorticoid activity when administered alone, but the same dose administered with aldosterone (1 .mu.g/100 g) doubled the mineralocorticoid response. Under identical conditions, cortisol was without effect. In the adrenalectomized rat kidney, in vitro, 5.alpha.-DHF had 20% the affinity of dexamethasone for classical (type II) glucocorticoid receptors, 10% the affinity of corticosterone for (type III) corticosteroid-binding globulin-like glucocorticoid receptors and 3% the affinity of aldosterone for mineralocorticoid receptors (type I). 5.alpha.-DHF had < 0.1% the affinity of dihydrotestosterone in mouse kidney receptors and < 0.1% the affinity of both estradiol and progesterone for their receptors in rat uterus. As 5.alpha.-DHF had low affinity for mineralocorticoid receptors and an effect (aldosterone amplification) totally outside the ambit of classical steroid effects, it may belong to a new physiological class of steroid hormones.