Dexamethasone regulates glutamine synthetase expression in rat skeletal muscles

Abstract

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.

Modeling of Corticosteroid Pharmacogenomics in Rat Liver Using Gene Microarrays

“…It is widely accepted that both enzymes were induced at the transcriptional level by CS-receptor complex binding to GRE (Max et al, 1988) and could be well captured by our fifth-generation model. Cluster Table 6, which also provides estimated model parameters.…”

Corticosteroid effects in skeletal muscle: Gene induction/receptor autoregulation

“…MPL is cleared from the blood in a biexponential manner, and is undetectable in plasma by 8 h postinjection. 3 The rapid return of GS message to baseline indicates that the chronic presence of the drug is necessary to accumulate the increased message levels observed by Max 10 and others. [4][5][6] The results suggest that the wave of GS message and enzyme is initiated by a steroid-induced increase in the rate of message synthesis while the rate of message degradation remains constant; the wave of message is terminated when the rate of transcription returns to the predrug level.…”

Steroid Myopathy: Pathogenesis and Effects of Growth Hormone and Insulin-Like Growth Factor-I Administration

“…The molecular mechanisms that regulate glutamine synthetase expression in muscle remain to be clarified. Steroids enhance glutamine synthetase activity in the skeletal muscle [12, 13]. The glutamine synthetase gene has been shown to contain a composite glucocorticoid response element [14, 15].…”