Glucocorticoids inhibit precursor incorporation into protein in splenic lymphocytes by stimulating protein degradation and expanding intracellular amino acid pools.
In the presence of tracer concentrations of extracellular leucine (5 microM), treatment of rat splenic lymphocyte suspensions in vitro with 1 microM dexamethasone for 2.5-4 h caused a 30-35% inhibition of [3H]leucine incorporation into protein. As the extracellular leucine concentration was raised to 5mM, this inhibition was progressively reduced to 0-12%. This phenomenon correlated with a marked dependence on extracellular leucine concentration of the dexamethasone-dependent enlargement of free intracellular leucine pools in splenic lymphocytes: a 123% increase in pool size with tracer extracellular leucine; a 10% increase with 5 mM leucine. Varying extracellular leucine had no effect on: (1) nuclear [3H]dexamethasone binding by the cells; (2) the concentration of dexamethasone needed for half-maximal inhibiton of [3H]leucine incorporation; (3) the time course of onset and maximal expression of the hormonal inhibition of [3H]leucine incorporation; or (4) the magnitude of dexamethasone-dependent inhibition of [3H]uridine incorporation into RNA by these cells. There was no detectable effect of dexamethasone on uptake and retention of [3H]leucine by the cells regardless of the extracellular leucine concentration. Treatment of splenic lymphocytes for 4 h in vitro with 1 microM dexamethasone caused a small shift of ribosomes from larger aggregate polysomes to smaller forms. Thus, glucocorticoid-induced inhibition of amino aicd incorporation in splenic lymphocytes is a multicomponent response, of which an actual decrease in protein synthesis is only a small part. Enlargement of free intracellular amino acid pools, probably resulting from increased protein degradation, is the major contributing factor to the hormonal inhibition of amino acid incorporation.
D000596:Amino Acids / Q000378:metabolism*; D000818:Animals; D001692:Biological Transport; D002467:Cell Nucleus / Q000378:metabolism; D003907:Dexamethasone / Q000378:metabolism / Q000494:pharmacology*; D007700:Kinetics; D007930:Leucine / Q000378:metabolism; D008214:Lymphocytes / Q000187:drug effects / Q000378:metabolism*; D011132:Polyribosomes / Q000187:drug effects / Q000378:metabolism; D014176:Protein Biosynthesis; D011506:Proteins / Q000235:genetics; D051381:Rats; D011965:Receptors, Glucocorticoid / Q000378:metabolism; D013154:Spleen / Q000378:metabolism
D000596:Amino Acids; D011506:Proteins; D011965:Receptors, Glucocorticoid; C028697:dexamethasone receptor; D003907:Dexamethasone; D007930:Leucine