RELATIONSHIP BETWEEN PLASMA ADRENOCORTICOTROPIN, HYPOTHALAMIC OPIOID TONE, AND PLASMA LEPTIN

The purpose of the present study was to further the understanding of t he relationship between plasma leptin concentrations, hypothalamic opi oid tone, and plasma ACTH secretory dynamics. ACTH(1-24) challenges (2 50 mu g) produced the expected increase in plasma cortisol levels but did not alter plasma leptin levels. Activation of the entire hypothala mic-pituitary-adrenal (HPA) axis was induced by employing the opioid r eceptor antagonist, naloxone. By blocking opioidergic inhibitory input to hypothalamic CRH neurons, naloxone induced the expected increase i n plasma ACTH and cortisol. Plasma ACTH levels peaked 30 min after nal oxone administration, whereas plasma cortisol levels peaked 60 min aft er opioid receptor blockade. Once again, plasma leptin concentrations were not altered by this manipulation. However, there was a positive c orrelation between fasting, integrated plasma leptin concentrations, a nd plasma ACTH responses to naloxone (peak r = 0.822, P < 0.0001; and area under curve r = 0.832, P < 0.0001). The correlation was stronger when leptin was normalized to body mass index and expressed as the lep tin/body mass index ratio (peak r = 0.878, P < 0.00001; and area under curve r = 0.882, P < 0.00001). In summary, these findings indicate th at activation of the HPA axis does not acutely alter plasma leptin con centrations. However, plasma leptin levels may influence hypothalamic opioidergic tone and thus modulate the magnitude of CRH release. The a cute interaction of the HPA axis and leptin is unidirectional.