Dopamine effects on 11-deoxycorticosterone concentrations in patients with Cushing's syndrome and in vitro

The effect of dopamine (1 micrograms/kg/min by i.v. infusion) on corticosteroid levels was studied in five patients with cortisol excess caused by increased ACTH secretion. In four of the five subjects dopamine, when compared with placebo infusion, caused plasma concentrations of 11-deoxycorticosterone to rise without affecting levels of cortisol, corticosterone or aldosterone. In a parallel in-vitro study using incubations of bovine adrenal zona glomerulosa cells, dopamine (10(-9) mol/l-10(-5) mol/l) had no effect on basal or ACTH stimulated secretion of aldosterone, cortisol or 11-deoxycorticosterone. However, dopamine (10(-5) mol/l) partially inhibited angiotensin II (10(-7) mol/l) stimulated secretion of aldosterone (4.36 ng/10(6) cells/h +/- 0.28 vs 2.90 +/- 0.20, P less than 0.05) but did not alter 11-deoxycorticosterone secretion i the same incubations. these data suggest that the effect of dopamine on 11-deoxycorticosterone secretion in vivo may not be due to its direct action on the adrenal to inhibit corticosteroidogenesis. An alternative explanation is that dopamine may alter extra-adrenal synthesis of 11-deoxycorticosterone, possibly by increasing substrate availability to tissues capable of 21-hydroxylation reactions.