Acute effects of orexins A and B on the rat pituitary-adrenocortical axis

Orexins A and B are hypothalamic peptides, which act through two receptor s ubtypes, called OX1R and OX2R. They belong to a group of neuropeptides invo lved in the central regulation of food intake, members of which (neuropepti de Y and leptin) are known to modulate the function of the pituitary-adreno cortical axis (PAA). We examined the effects at 60 and 120 min of a subcuta neous injection of 5 or 10 nmol/kg of orexins on the function of the rat PA A. Orexin-A raised plasma concentrations of ACTH, aldosterone and corticost erone at both 60 and 120 min, corticosterone response being the most intens e one. Orexin-B evoked a sizeable decrease in the plasma level of ACTH, wit hout changing that of corticosterone. The effect of orexin-B on aldosterone plasma concentration was biphasic, the lower dose decreasing and the highe r one increasing it at both 60 and 120 min. Evidence indicates that OX1R bi nds both orexins, while OX2R is selective for orexin-B, and that only OX2R is present in the hypothalamic nucleus paraventricularis. On these grounds, our findings allow us to conclude: (i) OX1R stimulates and OX2R inhibits r at PAA; (ii) orexin-A stimulates PAA, the activation of OX1R prevailing ove r that of OX2R, while orexin-B suppresses PAA function; and (iii) the aldos terone-secreting response to the higher dose of orexin-B may probably be as cribed to the activation of one or more extra-PAA mechanisms enhancing secr etory activity of the zona glomerulosa.