Mineralocorticoid activity of 16β-hydroxydehydroepiandrosterone and related steroids

16β-Hydroxydehydroepiandrosterone (16β-OH-DHEA) and related C₁₉-steroids have recently been reported to be etiologic in low-renin essential hypertension. The mineralocorticoid potency of 16β-OH-DHEA and several C₁₉-steroids (16-oxo-A-diol, 16-oxo-testosterone, 16β-OH-epiandrosterone, 5-androstene-3β, 16β, 17β-triol, 16β-OH-testosterone, 18-OH-DHEA, and 16α-OH-DHEA) were investigated in two different rat bioassay systems under a variety of experimental conditions. In all but one instance, only negligible mineralocorticoid activity was observed, usually less than 0.1 per cent that of aldosterone. Since 16β-OH-DHEA has negligible mineralocorticoid activity in the rat bioassay and the toad bladder assay (as reported by others), does not cause hypertension when injected chronically into the rat, and does not displace aldosterone from its renal receptors, it appears unlikely to be etiologic in low-renin essential hypertension. On the other hand, when 16-oxo-testosterone was injected intraperitoneally instead of subcutaneously, it demonstrated a slight increase in mineralocorticoid activity (from < 0.1 per cent to 0.2 per cent) which equaled that of 18-hydroxydeoxycorticosterone (18-OH-DOC) injected subcutaneously. Thus, the possibility remains that 16-oxo-testosterone or a closely related metabolite may have sufficient mineralocorticoid activity to be involved in certain forms of hypertension in man.