Reduction of glutamine synthetase mRNA in hypertrophied skeletal muscle.

Skeletal muscle glutamine synthetase (GS) expression is reduced by endurance exercise and is increased when normal innervation is interrupted. This investigation was undertaken to determine whether GS expression is downregulated by the increased contractile activity associated with functional overload. Plantaris muscles overloaded for 30 days by synergist ablation were 70% heavier than those in sham-operated and unoperated control muscles. GS mRNA levels from hypertrophied muscles, measured by Northern and dot-blot hybridization, were reduced to 30% of controls. Changes in total RNA concentration and the proportion of poly(A)+ RNA in the total RNA pool did not account for the decline in GS mRNA. Despite reduced levels of GS mRNA, GS enzyme activity (nmol.h-1.mg protein-1) was unchanged in the hypertrophied muscles (overload, 79 +/- 5; control, 82 +/- 4). To further examine the lack of relationship between GS mRNA and enzyme activity, the concentration of glutamine, a known posttranslational modifier of GS activity, was measured. Consistent with the observed enzyme activities, muscle glutamine was unchanged in hypertrophied muscle (overload, 6.2 +/- 0.3; control, 5.8 +/- 0.4 mumol/g tissue). These results suggest that translational or posttranslational regulation, other than through alterations in glutamine concentration. may play a role in maintaining GS enzyme levels in hypertrophied muscle. Moreover, the regulation of GS activity in muscle hypertrophy may differ from the regulation with endurance training, in which changes in enzyme activity parallel changes in mRNA.