19-nordeoxycorticosterone and 19-hydroxydeoxycorticosterone

Excess mineralocorticoid activity is thought to be responsible for the increased sodium reabsorption found after adrenal enucleation, but no known mineralocorticoid has been demonstrated in quantities sufficient to account for this antinatriuresis. 19-Hydroxydeoxycorticosterone (19-OH-DOC) has been synthesized by the incubated enucleate adrenal capsule and 19-nordeoxycorticosterone (19-nor-DOC), a possible metabolite, has been found in the urine of rats with regenerating adrenal glands. To evaluate the in vivo mineralocorticoid potency of these steroids, we studied glucocorticoid-replete adrenalectomized rats and measured the sodium and potassium excretion after administration of these steroids. Our results indicate that 19-nor-DOC has equipotent antinatriuretic activity compared to aldosterone but was less kaluretic. 19-OH-DOC had no significant antinatriuretic or kaluretic activity. We conclude that 19-nor-DOC is a potent mineralocorticoid and may be responsible for the enhanced sodium reabsorption found after adrenal enucleation.

Topics: Adrenalectomy; Animals; Desoxycorticosterone; Male; Mineralocorticoids; Potassium; Rats; Sodium

Adrenal enucleation is followed by a period of increased sodium reabsorption thought to be due to excess mineralocorticoid activity. However, it has not been demonstrated that increased production of any known mineralocorticoid accounts for this antinatriuresis. Recently, 19-hydroxydeoxycorticosterone (19-OH-DOC) was found in incubates of regenerating adrenal capsules 3-4 days postenucleation and 19-nordeoxycorticosterone (19-nor-DOC) was identified in the urine of rats with regenerating adrenals. Because it was possible that these hormones might play a role in the sodium retention after adrenal enucleation, we compared the mineralocorticoid activity of these steroids to aldosterone using the toad bladder. Using short-circuit current as a measure of sodium transport, we found that 19-OH-DOC (10(-8) M) had no significant effect on sodium transport. However, 19-nor-DOC (10(-8) M) increased sodium transport to a degree not different from aldosterone (10(-8) M). Furthermore, the onset of action, duration of activity, and inhibition of effect of 19-nor-DOC by spironolactone were not different from that of aldosterone. We conclude that 19-nor-DOC exhibits a significant effect on sodium transport and thus has the potential to play a role in the sodium retention following adrenal enucleation. Under the conditions of these studies, 19-OH-DOC exhibited no effect on sodium transport.

Topics: Aldosterone; Animals; Biological Transport, Active; Bufo marinus; Desoxycorticosterone; Kinetics; Sodium; Spironolactone; Urinary Bladder