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Title: Glucocorticoids inhibit precursor incorporation into protein in splenic lymphocytes by stimulating protein degradation and expanding intracellular amino acid pools. Author: MacDonald RG, Cidlowski JA. Journal: Biochim Biophys Acta; 1982 Aug 06; 717(2):236-47. PubMed ID: 7115767. Abstract: 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.[Abstract] [Full Text] [Related] [New Search]