The role of corticotropin-releasing factor and urocortin in the modulation of ingestive behavior.

ABSTRACT

Participation of the hypothalamo-pituitary-adrenocortical axis, and its primary brain trigger, corticotropin-releasing factor (CRF) in the control of ingestive behavior can be inferred from data suggesting that CRF and its homologue urocortin act in brain to limit appetite following administration in rodents. Moreover, levels of endogenous CRF, CRF(1)and CRF(2)receptors and CRF-binding protein, which sequesters CRF and urocortin, are altered by changes in nutritional status brought about by food restriction/repletion. Mediation of the anorexic effects of CRF and urocortin appear not to privilege CRF(1)receptors, unlike the anxiogenic effects of CRF which are primarily a consequence of CRF(1)receptor activation. Such fear-like consequences of CRF system activation constitute a non-specific mechanism whereby the emergence of behaviors incompatible with food intake may appear to suppress appetite without affecting hunger per se. However, enhanced appetite following administration of CRF receptor antagonists and the involvement of CRF systems in sexual appetite and drug-seeking behavior all suggest a role for CRF in ingestive behavior. In particular, available evidence suggests that physiologically relevant suppression of appetite may accompany CRF system activation occurring as a consequence of stressor exposure induced by nutrient imbalance, for example, or under conditions of excessive intake or consumption of unfamiliar foodstuffs.