Effects of glucocorticoids on glutamine metabolism in skeletal muscle

The effects of dexamethasone on nitrogen and amino acid metabolism in the dog were studied in order to gain insight into the role of glucocorticoids in accelerated proteolysis and altered metabolism of glutamine in catabolic illnesses. After dexamethasone administration at a dose of 0.44 mg X day-1 X kg-1, nitrogen balance shifted from slightly positive (+0.126 g N X day-1 X kg-1) to markedly negative (-0.278 g N X day-1 X kg-1). This was associated with a 23% fall in total free amino acid nitrogen in skeletal muscle, with 80% of the decline accounted for by a decrease in glutamine. Plasma glutamine concentration decreased by 26%, although total plasma free amino acid nitrogen was unchanged because of a 49% increase in alanine. The alterations in intracellular and circulating levels of glutamine were not accompanied by measurable changes in glutamine synthetase or glutaminase activities in skeletal muscle. Hindquarter amino acid flux measurements demonstrated that the decline in intracellular glutamine concentration was associated with a marked increase in glutamine efflux from skeletal muscle. This occurred in spite of minimal changes in the intracellular/extracellular glutamine gradient. It is concluded that accelerated muscle glutamine release caused by glucocorticoids is a major contributor to the decreased glutamine levels in muscle that occur during critical illnesses.