Inhibition of Glucose Uptake in Lymphosarcoma P1798 by Cortisol and Its Relationship to the Biosynthesis of Deoxyribonucleic Acid

The biochemical basis for the action of glucocorticoids on lymphoid tissue has been studied using cell suspensions of the cortisol-sensitive and -resistant lines of lymphosarcoma P1798. Comparison of these tumors indicated that exposure to physiological doses of glucocorticoids produces a significant inhibition of thymidine-3H incorporation into tumor DNA and of uniformly labeled glucose-14C uptake only in the sensitive line. Using 2-deoxy-d-glucose-1-14C, it was found that cortisol causes an inhibition of uptake or phosphorylation of this analogue. Impairment of glucose uptake is significant within 1 hour and at this time is greater than the inhibition of thymidine incorporation into DNA. When glucose is omitted from the medium, thymidine uptake into DNA is reduced by 80 to 90%, and under these conditions the inhibitory action of cortisol on thymidine incorporation is half of that seen in the complete medium. Omission of amino acids from the incubation medium resulted in a 50% decrease of glucose uptake into whole cells and also reduced the inhibition produced by cortisol. These findings provide additional support for the concept that reduced energy utilization may be of significance in mediating the physiological action of glucocorticoids on lymphoid tissues.