Glucocorticoid Action on Rat Thymus Cells

Continued maximal levels of incorporation of amino acids into protein in rat thymus cell suspensions require added glucose, a requirement only partially satisfied by other readily metabolized carbohydrate substrates such as pyruvate and lactate. Effects of substrates on incorporation rates correlate with their ability to generate small elevations in ATP above the levels in controls without substrate. The stimulatory effect of glucose occurs prior to its conversion to intracellular pyruvate. The effects of glucose, and other carbohydrates as well, also correlate with glucose 6-phosphate levels. The data suggest a stimulatory role for glycolytic intermediates on amino acid incorporation, mediated possibly through the effects of glycolysis on adenine nucleotides. Cortisol addition leads to an early inhibition of only the carbohydrate-dependent amino acid incorporation into protein. This hormone effect is associated with a cortisol inhibition of the ability of glucose and other carbohydrates to generate ATP, the effects on ATP in some instances preceding the effects on incorporation. With glucose as substrate, effects of cortisol on amino acid incorporation may be attributed to a prior inhibition of glucose uptake; with lactate and pyruvate as substrate, effects on substrate uptake and on the initial metabolic steps were not found. Although the inhibition of glucose uptake is not the unique action of cortisol, the results suggest that hormonal inhibition at this site has considerable physiological significance.