Orexins in the regulation of the hypothalamic-pituitary-adrenal axis

Pharmacological Reviews
Raffaella SpinazziG G Nussdorfer

Abstract

Orexin-A and orexin-B are hypothalamic peptides that act via two G protein-coupled receptors, named orexin type 1 and type 2 receptors (OX1-Rs and OX2-Rs). The most studied biological functions of orexins are the central control of feeding and sleep, but in the past few years findings that orexin system modulates the hypothalamic-pituitary-adrenal (HPA) axis, acting on both its central and peripheral branches, have accumulated. Orexins and their receptors are expressed in the hypothalamic paraventricular nucleus and median eminence and orexin receptors in pituitary corticotropes, adrenal cortex, and medulla. Whereas the effects of orexins on adrenal aldosterone secretion are doubtful, compelling evidence indicates that these peptides enhance glucocorticoid production in rats and humans. This effect involves a 2-fold mechanism: 1) stimulation of the adrenocorticotropin-releasing hormone-mediated pituitary release of adrenocorticotropin, which in turn raises adrenal glucocorticoid secretion; and 2) direct stimulation of adrenocortical cells via OX1-Rs coupled to the adenylate cyclase-dependent cascade. The effects of orexins on catecholamine release from adrenal medulla are unclear and probably of minor relevance, but there are i...Continue Reading

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