ENHANCEMENT OF GLUCOCORTICOID RECEPTOR-MEDIATED GENE-EXPRESSION BY CELLULAR STRESS - EVIDENCE FOR THE INVOLVEMENT OF A HEAT SHOCK-INITIATEDFACTOR OR PROCESS DURING RECOVERY FROM STRESS

Recent reports have demonstrated the ability of cellular stress to cau se a large increase in the maximal levels of steroid receptor-mediated gene expression, a process we refer to as the heat shock potentiation effect (HSPE). In the present work, we have analyzed the time of appe arance of the HSPE on the glucocorticoid receptor (GR) of L929 cells s tably-transfected with the MMTV-CAT reporter plasmid (LMCAT2 cells). I n LMCAT2 cells exposed to heat shock (43 degrees C, 2-h) before additi on of 1 mu M dexamethasone, the first appearance of HSPE (CAT levels g reater than hormone-alone) occurred at 8 h of recovery and continued t o increase by 24 h of recovery. Treatment of LMCAT2 cells with 1 mu M dexamethasone for 2 h before heat or chemical shock (sodium arsenite) resulted in the same delayed onset pattern for the HSPE. Based on a [S -35]methionine assay and tests of L929 cells stably transfected with t he constitutive pSV2-CAT reporter, evidence is provided that the delay ed appearance of the HSPE is not due to the heat shock block of genera l protein synthesis or to specific repression of CAT mRNA expression o r translation. By using short-term incubations (4 h) with dexamethason e during the recovery period, the peaks of HSPE expression during reco very were determined to be 12-16 h for CAT enzyme activities, and 4-8 h for CAT mRNA expression. Taken together, these results provide evide nce that the timing of the HSPE is not dependent on the rate of GR act ivation, or on the type of stress, but rather on a factor or process t hat is either synthesized or activated during the recovery period foll owing stress.