Glutamine interferes with glucocorticoid-induced expression of glutamine synthetase in skeletal muscle

Abstract

Skeletal muscle atrophy from glucocorticoids is prevented by glutamine infusion. Because the gene-encoding glutamine synthetase (GS) is glucocorticoid inducible, it represented an appropriate model for resting whether glucocorticoids and glutamine exert opposing actions on the expression of specific genes related to atrophy in muscle tissue. Rats were administered hydrocortisone 21-acetate or the dosing vehicle (carboxymethyl cellulose) and were infused with saline (Sal) or glutamine (Gln, 240 mM, 0.75 ml/h) for 7 days. Hormone treatment did not significantly lower glutamine levels in fast-twitch white or red regions of the quadriceps. Despite higher serum glutamine concentrations with amino acid infusion [1.52 +/- 0.03 (Gln) vs. 1.20 +/- 0.04 (Sal) mumol/ml], muscle glutamine concentrations were not markedly increased in these fiber types. In saline-infused animals, glucocorticoid treatment produced 200-300% increases in plantaris, fast-twitch white, and fast-twitch red muscle GS enzyme activity and mRNA. Moreover, in all muscle types studied, glutamine infusion diminished glucocorticoid effects on GS enzyme activity to 131-159% and on GS mRNA to 110-200% of the values in saline-treated controls. These data demonstrate that glutamine infusion results in inhibiting GS expression, but the absence of changes in muscle glutamine concentration suggests the interplay of additional regulators of the GS gene.