GLUCOCORTICOIDS RECIPROCALLY REGULATE EXPRESSION OF THE CCAAT ENHANCER-BINDING PROTEIN-ALPHA AND PROTEIN-DELTA GENES IN 3T3-L1 ADIPOCYTES AND WHITE ADIPOSE-TISSUE/

Glucocorticoid agonists, i.e. dexamethasone or triamcinolone acetonide , rapidly induce expression of CCAAT/enhancer-binding protein (C/EBP) delta and repress expression of C/EBP alpha in fully differentiated 3T 3-L1 adipocytes. Within 30 min of glucocorticoid treatment, the cellul ar level of C/EBP delta rises dramatically, increasing >100 fold withi n 6 h. Concurrently, the level of C/EBP alpha decreases, reaching a mi nimum within 4 h. The dexamethasone concentration dependence and stero id specificity of these responses suggest that both processes are medi ated by the glucocorticoid receptor. The reciprocal effects of dexamet hasone on the steady-state levels of C/EBP alpha and C/EBP delta can b e accounted for kinetically and quantitatively by changes in their mRN A levels and by the transcription rates of their respective genes. The glucocorticoid-induced changes in expression of the C/EBP isoforms ar e correlated with the transcriptional activation of the SCD1 gene, an adipocyte gene known to be transactivated by C/EBP isoforms. Glucocort icoids also regulate expression of the C/EBP isoforms in vivo. Within 4 h of administration of dexamethasone or triamcinolone acetonide to a dult rats, expression of C/EBP delta is induced in white adipose tissu e while expression of C/EBP alpha is repressed. Like the response in 3 T3-L1 adipocytes, the effects of dexamethasone on C/EBP alpha in white adipose tissue are rapid and transient.