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Elevated conversion rates of cortisol to 5α-dihydrocortisol (5α-DHF) have been found in a child with hypoaldosteronism, Na⁺ retention, hypokalemic alkalosis, and hypertension. Studies investigating possible etiological roles for 5α-DHF have shown in the rat urinary electrolyte bioassay in vivo that 5α-DHF (30–100 μg/100 g) has minimal mineralocorticoid activity when administered alone, but the same dose administered with aldosterone (1 μg/100 g) doubles the mineralocorticoid response. Under identical conditions, cortisol was without effect. In the adrenalectomized rat kidney, in vitro, 5α-DHF has 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). 5α-DHF has <0.1% the affinity of dihydrotestosterone in …