The regulation of glutamine synthetase expression by dexamethasone was studied in rat skeletal muscles. Daily administration of dexamethasone caused striking enhancement of glutamine synthetase activity in plantaris, soleus, and diaphragm muscles. Northern blot analysis revealed that the dexamethasone-mediated increase of glutamine synthetase activity was associated with dramatically increased levels of glutamine synthetase mRNA. Both glutamine synthetase activity and mRNA levels were significantly elevated in plantaris muscle at 0.5 mg.kg-1.day-1 of dexamethasone, a dose that approximates endogenous corticosteroid levels in animals under severe stress. Quantification of changes in glutamine synthetase mRNA on the basis of total mRNA (by oligo dT hybridization) also revealed a major increase in glutamine synthetase mRNA. Dexamethasone was without effect on beta-tubulin mRNA levels, indicating that glutamine synthetase induction is not part of a global response to glucocorticoids. Dexamethasone treatment resulted in only an approximately 15% increase in glutamine synthetase activity in heart; there was no change in glutamine synthetase mRNA level in this tissue. Thus glucocorticoids regulate glutamine synthetase gene expression in rat skeletal muscles.
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