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 subtypes, called OX1R and OX2R. They belong to a group of neuropeptides involved in the central regulation of food intake, members of which (neuropeptide Y and leptin) are known to modulate the function of the pituitary-adrenocortical axis (PAA). We examined the effects at 60 and 120 min of a subcutaneous injection of 5 or 10 nmol/kg of orexins on the function of the rat PAA. Orexin-A raised plasma concentrations of ACTH, aldosterone and corticosterone at both 60 and 120 min, corticosterone response being the most intense one. Orexin-B evoked a sizeable decrease in the plasma level of ACTH, without changing that of corticosterone. The effect of orexin-B on aldosterone plasma concentration was biphasic, the lower dose decreasing and the higher one increasing it at both 60 and 120 min. Evidence indicates that OX1R binds 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 rat PAA; (ii) orexin-A stimulates PAA, the activation of OX1R prevailing over that of OX2R, while orexin-B suppresses PAA function; and (iii) the aldosterone-secreting response to the higher dose of orexin-B may probably be ascribed to the activation of one or more extra-PAA mechanisms enhancing secretory activity of the zona glomerulosa.