Relationship between plasma adrenocorticotropin, hypothalamic opioid tone, and plasma leptin

The purpose of the present study was to further the understanding of the relationship between plasma leptin concentrations, hypothalamic opioid tone, and plasma ACTH secretory dynamics. ACTH(1-24) challenges (250 micrograms) produced the expected increase in plasma cortisol levels but did not alter plasma leptin levels. Activation of the entire hypothalamic-pituitary-adrenal (HPA) axis was induced by employing the opioid receptor antagonist, naloxone. By blocking opioidergic inhibitory input to hypothalamic CRH neurons, naloxone induced the expected increase in plasma ACTH and cortisol. Plasma ACTH levels peaked 30 min after naloxone administration, whereas plasma cortisol levels peaked 60 min after opioid receptor blockade. Once again, plasma leptin concentrations were not altered by this manipulation. However, there was a positive correlation between fasting, integrated plasma leptin concentrations, and 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 leptin/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 that activation of the HPA axis does not acutely alter plasma leptin concentrations. However, plasma leptin levels may influence hypothalamic opioidergic tone and thus modulate the magnitude of CRH release. The acute interaction of the HPA axis and leptin is unidirectional.