Regulation of 18-oxocortisol and 18-hydroxycortisol by the Renin-angiotensin System and ACTH in Man

Based on urinary excretion studies the secretion of the cortisol derivatives, 18-oxocortisol and 18-hydroxycortisol are believed to be regulated by ACTH and to a lesser degree by the renin-angiotensin system. Plasma concentrations of 18-oxocortisol and 18-hydroxycortisol were measured during the simultaneous activation of the renin-angiotensin system and inhibition of ACTH secretion. Five healthy male subjects consuming a sodium diet ad libitum were studied. Blood was drawn at 0800 h after 1 h in the supine position. In the first set of experiments, the subjects remained in the supine position from 0800 to 1000 h with or without the oral administration of 2 mg dexamethasone at 0800 h. In the second set of experiments the subjects were placed in the upright position after drawing the 0800 h sample. The subjects were studied with and without dexamethasone administered at 0800 h. Blood was drawn again at 1000 h. Plasma levels of 18-oxocortisol, 18-hydroxycortisol, ACTH, plasma renin activity (PRA), cortisol, aldosterone and 18-hydroxycorticosterone were measured by radioimmunoassay. None of these parameters changed during the 2 h in the supine position. 18-Oxocortisol, 18-hydroxycortisol, aldosterone, 18-hydroxycorticosterone and PRA increased, but ACTH and cortisol did not change when the subjects were placed in the upright position. After dexamethasone administration, 18-oxocortisol, 18-hydroxycortisol, cortisol, aldosterone and 18-hydroxycorticosterone decreased in the supine position and no increase occurred in 18-oxocortisol, 18-hydroxycortisol and 18-hydroxycorticosterone in the upright position. PRA and aldosterone increased and ACTH and cortisol decreased in these subjects. 18-Oxocortisol and 18-hydroxycortisol were more dependent on ACTH regulation and less on the renin-angiotensin system than aldosterone.