Glucocorticoids regulate rat glutamine synthetase expression in a tissue-specific manner

Abstract

During stress states, organismal glutamine production is augmented secondary to an increase in the activity of glutamine synthetase (GS) in the lung and skeletal muscle. Because glucocorticoids are key regulators of the metabolic response to stress, we undertook a survey of glucocorticoid induction of GS expression in rat organs in response to dexamethasone. Male adult rats were injected with glucocorticoid or vehicle and 4 hr later, 10 organs were assayed for GS messenger RNA and protein contents by Northern and Western blotting. We observed a 20-fold range of GS mRNA levels in organs of control animals. Blotting detected two GS RNA species of approximately 2.8- and 1.4-kb sizes in all tissue except testis, where an additional 2-kb RNA species was observed. Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) mRNA levels were also assayed and used as a normalization factor. An approximately 10-fold range of GAPDH mRNA levels was observed. Four hours after dexamethasone injection, a nearly a 5-fold increase in glutamine synthetase mRNA levels in lung and muscle, as well as an approximately 2-fold increase in heart were observed. Relative to GAPDH mRNA, a significant decrease in GS mRNA levels was observed in the liver. A wide range of glutamine synthetase protein contents were observed in rat organs. Comparison of Northern and Western blotting results revealed a dichotomy in the ratio of relative GS mRNA and protein level in rat organs, suggesting that tissue-specific posttranscriptional processes determine GS protein levels.(ABSTRACT TRUNCATED AT 250 WORDS)