16Beta-hydroxydehydroepiandrosterone: the dichotomy between renal receptor binding and urinary electrolyte activity.
Excessive production of 16beta-hydroxydehydroepiandrosterone (16beta-OH-DHEA) has been suggested as a cause of low-renin essential hypertension. The mineralocorticoid effect of 16beta-OH-DHEA was reported to be one-fortieth that of aldostereone in the rat bioassay. Using kidney slices from adrenalectomized rats, the affinity of 16beta-OH-DHEA and a series of related compounds for mineralocorticoid receptors has been determined. In studies done at both 4 C and 37 C, the affinity of 16beta-OHDHEA for mineralocorticoid receptors was found to be less than 0.1% that of aldosterone (P less than 0.01). Various related steroids and/or potential metabolites similarly showed negligible affinity for the aldosterone receptor. In addition, In addition, 16beta-OHDHEA showed no significant affinity for renal dexamethasone-binding sites (Type II glucocorticoid receptors), corticosterone-binding sites (Type III glucocorticoid receptors), dihydrotestosterone binding sites, or estradiol binding sites. In in vivo competition experiments, the concurrent administration of 50 mug deoxycorticosterone reduced (3H)aldosterone binding to 20-30% of control levels; 50 mug 16beta-OH-DHEA did not compete for (3H)aldosterone binding sites. In in vivo bioassay electrolyte excretion was found-in contrast to that of aldosterone-to be variable. Within a given group, certain rats reproducibly responded to 16beta-OH-DHEA by sodium retention and kaliuresis; in others no response was observed. In vitro binding studies comparing "responders" with "non-responders" demonstrated that in neither group did 16beta-OH-DHEA have significant affinity for renal mineralocorticoid receptors. Accordingly, the mechanism whereby 16beta-OHDHEA produces changes in urinary electrolyte excretion appears independent of classical mineralocorticoid effector mechanisms. The conditions under which this effect is seen await eludication.
D000450:Aldosterone / Q000378:metabolism; D000818:Animals; D001667:Binding, Competitive; D003345:Corticosterone / Q000378:metabolism; D003687:Dehydroepiandrosterone / Q000378:metabolism*; D004573:Electrolytes; D004967:Estrogens / Q000378:metabolism; D005260:Female; D007668:Kidney / Q000378:metabolism*; D008297:Male; D051381:Rats; D011956:Receptors, Cell Surface
D004573:Electrolytes; D004967:Estrogens; D011956:Receptors, Cell Surface; D003687:Dehydroepiandrosterone; D000450:Aldosterone; D003345:Corticosterone