Lower weight loss and food intake in protein-deprived, corticotropin releasing hormone-deficient mice correlate with glucocorticoid insufficiency.

To determine if CRH and glucocorticoids are respectively required for hypophagia and catabolism in malnutrition, we have subjected wild-type (WT) and CRH knockout (KO) mice to dietary protein deprivation. Compared with WT mice, CRH KO mice exhibited greater decreases in food intake and negligible change in plasma corticosterone after 7 days of protein-free diet. Restricting consumption of normal or protein-free diet for 9 days to the lower intake in protein-deprived CRH KO mice increased evening plasma corticosterone in WT but not KO mice. Restricted intake of protein-free diet increased morning corticosterone more in both genotypes than restricted intake of normal diet, although corticosterone levels were much lower in CRH KO mice. CRH deficiency attenuated body and thymus weight loss induced by restricted diets. Lower weight loss in CRH KO mice was associated with lower fractional loss of body water and protein. The remaining catabolic response in CRH KO mice did not correlate with morning plasma catecholamines or insulin. Corticosterone, but not the progestational appetite stimulant megestrol acetate, prevented hypophagia in CRH KO mice given protein-free diet. We conclude that differences in feeding and metabolic responses to protein deprivation between WT and CRH KO mice are primarily attributable to glucocorticoid insufficiency.