HEPATIC EXPRESSION OF CCAAT ENHANCER BINDING-PROTEIN-ALPHA - HORMONALAND METABOLIC-REGULATION IN RATS/

There is a significant body of evidence which suggests that the alpha- isoform of the CCAAT/enhancer binding protein (C/EBP alpha) plays a ce ntral regulatory role in energy metabolism in the liver. However, ther e is little information available regarding regulation of its expressi on in this tissue. In this study, we examined the effect of hormones a nd diabetes on its expression in rat H4IIE hepatoma cells and in rat l iver. Treatment of H4IIE cells with dexamethasone led to a threefold i ncrease in C/EBP alpha mRNA within 4 h. Insulin treatment produced a b i-phasic response, initially reducing mRNA levels up to the 4 h time p oint, but after 8 h a twofold increase in C/EBP alpha mRNA was observe d. Treatment with 8-chlorophenylthio-cAMP produced a twofold induction of C/ EBP alpha mRNA after 8 h. Western analysis indicated that the c hanges in mRNA in response to hormonal treatment generally resulted in corresponding alterations in C/EBP alpha protein levels. Finally, we observed an inhibition of C/EBP alpha gene expression in streptozotoci n-diabetic rat liver, reflected by a decrease in both mRNA and protein levels that were partially reversed by insulin treatment. These resul ts indicate that the expression of C/EBP alpha in liver is under compl ex control by both hormonal and metabolic signals, which is consistent with its role as a trans-regulator of genes which play a role in ener gy metabolism.