EXERCISE INHIBITS GLUCOCORTICOID-INDUCED GLUTAMINE-SYNTHETASE EXPRESSION IN RED SKELETAL-MUSCLES

One purpose of this study was to determine whether the suppression of glucocorticoid-induced glutamine synthetase (GS) gene expression by exercise is localized to fiber types that are known to be primarily recruited during endurance running. A second purpose examined whether denervation, which is associated with a reduction in contractile activity, would upregulate GS expression. Exercise consisted of treadmill running at 31 m/min for 12-16 wk. Glucocorticoid treatment (100 mg/kg body wt hydrocortisone 21-acetate) was administered during the last 11 days of the exercise program. Basal GS expression was lowest (GS enzyme activity, 43 +/- 3 nmol.h-1.mg protein-1; GS mRNA, 1.0 arbitrary units) in the slow-twitch red soleus, a muscle type that is known to resist glucocorticoid-induced muscle wasting, intermediate (74 +/- 10 and 1.7 +/- 0.2) in fast-twitch red quadriceps, a muscle type susceptible to atrophy, and highest (106 +/- 16 and 5.4 +/- 1.3) in fast-twitch white quadriceps, a muscle type known to be most susceptible to atrophy. Hormone treatment increased GS enzyme activity and mRNA by two- to fourfold in all muscle types. Exercise diminished GS enzyme activity and mRNA in the fast-twitch red fibers to 35-70% of sedentary control values in both basal and glucocorticoid-stimulated muscles. The running also reduced GS enzyme activity in hormone-treated slow-twitch fibers but did not alter basal or glucocorticoid-induced GS expression in fast-twitch white fibers. These results indicate that glucocorticoids induce similar relative GS expression across all muscle types, but the low absolute levels of expression in slow-twitch muscles are not related to any atrophy. Of the fast-twitch types, glucocorticoid-mediated GS induction is suppressed by exercise in the red fibers but not the white, which is most likely because white fibers are not as active during prolonged submaximal activity. Denervation resulted in atrophy of the slow-twitch soleus muscles and an elevation of GS enzyme activity and mRNA. These data suggest that neural input contributes to basal GS expression.