Glucocorticoids and neuroendocrine function

Abstract

Recent experimental evidence supports the role of glucocorticoids in the neuroendocrine control of food intake and energy expenditure. In particular, glucocorticoids promote food consumption directly through stimulation of NPY and inhibition of CRH and melanocortin release. CRH and NPY are also functionally linked by a mutual regulation. CRH is anorexigenic when secreted acutely while it exerts the opposite effect when, upon sustained secretion, it stimulates the hypothalamo–pituitary–adrenal (HPA) axis. The orexigenic effects of glucocorticoids are counteracted by a steroid-induced rise in leptin levels that closes a regulatory loop regarding food consumption. Furthermore, glucocorticoids may alter body fat distribution, increasing truncal adiposity both directly and by inhibition of growth hormone secretion. No clearcut alterations of the HPA function are apparent in obesity as a whole. However, subtle and specific abnormalities may be noted in subsets of obese patients. Indeed, obesity, mostly visceral type, is associated with an increased cortisol clearance and 11-β hydroxysteroid dehydrogenase activity in the omental fat. In the same vein, an increased cortisol rise following a mixed meal has been observed in obese subjects. Finally, it has been proposed that adrenal incidentalomas, often characterized by enhanced cortisol secretion, might be a clinical expression of the X syndrome.