Effect of leptin on ACTH-stimulated secretion of cortisol in rhesus macaques and on human adrenal carcinoma cells

Objective: Because glucocorticoids stimulate leptin release and, at least i n vitro, leptin inhibits cortisol secretion, a feedback system between gluc ocorticoids and leptin has been proposed, However, in humans and non-human primates there are no ill vivo studies to support any role for leptin in th e control of the hypothalamic-pituitary-adrenal axis. In this study, we inv estigated the effect of leptin on ii) ACTH-stimulated secretion of cortisol in six male rhesus monkeys and (ii) basal and forskolin (FSK)-stimulated c ortisol secretion by the human adrenal carcinoma cell H295R in vitro. Design and Methods: In vivo studies: after suppression of endogenous ACTH w ith either dexamethasone (n = 6) or a corticotropin-releasing factor (CRF) antagonist (D-Phe CRF(12-41)) (n = 3), 1 mu g bolus of human ACTH(1-24) was administered to stimulate adrenal cortisol release. Blood samples were col lected every 15 min for 3 h. Leptin (1 mg) was infused over 4 h, starting 1 h before ACTH bolus. In vitro studies: NCI-H295R cells were incubated for 6, 12, 24 and 48 h in the absence or presence of 30 mu mol/l FSK in combina tion with leptin (100 ng/ml medium). Cortisol levels in serum and medium we re measured by solid phase radioimmunoassay. Results: Acute leptin infusion to rhesus monkeys did not change basal corti sol levels, peak cortisol levels after ACTH(1-24) or the area under the cur ve when compared with studies in which leptin was not given. FSK increased cortisol levels in medium at 24 and 48 h, but leptin did not change cortiso l release in either control or FSK-stimulated cells. Conclusions: Short-term leptin infusion affected neither the cortisol respo nse to ACTH in non-human primates in vivo nor cortisol release (basal or FS K stimulated) by H295R cells, in vitro. These data suggest that leptin may not be an acute regulator of primate adrenal cortisol secretion.