Glutamine synthetase induction by glucocorticoids in the glucocorticoid-sensitive human leukemic cell line CEM-C7

Abstract

Treatment of CEM‐C7 cells with glucocorticoids produces a 2.5‐fold increase in the activity of the enzyme glutamine synthetase (GS). This increase is specific for steroids with glucocorticoid activity and occurs over a range of steroid concentrations consistent with a receptor‐mediated mechanism. Half‐maximal and maximal inductions by dexamethasone (dex) occur at 2 × 10⁻⁸M and 2 × 10⁻⁷ M dex, respectively, concentrations approximately equal to those necessary to produce half and full occupancy of glucocorticoid receptors. GS activity began to increase 1 hour after dex treatment and was complete by 12 hours. This is well before any of the growth inhibitory or cytolytic effects of dex on this cell line occur. This increase was dependent on the presence of glucocorticoid receptors and required both RNA and protein synthesis. Removal of dex following stimulation to maximal levels resulted in a decrease of GS activity to preinduced levels with a half‐time of 5 hours. Glutamine deprivation of cells resulted in increased GS activity. However, even in the total absence of glutamine, dex treatment elicited a 2.0–2.5‐fold increase in GS activity, ruling out inhibition of glutamine uptake as a mechanism for the dex‐induced increase. Experiments with 5′‐bromodeoxyuridine (BrdU) demonstrated that GS elevation was sensitive to BrdU substitution of DNA, while dex‐induced growth inhibition was not. Therefore GS elevation and growth inhibition in this cell line appear to be independently expressed steroid responses.