Induction of the C/EBPβ Gene by Dexamethasone and Glucagon in Primary-Cultured Rat Hepatocytes

Abstract

The synthetic glucocorticoid, dexamethasone, and glucagon cooperatively elevated the level of mRNA for the transcription factor CCAAT/enhancer binding protein β (C/EBPβ) in primary-cultured rat hepatocytes. In response to dexamethasone and/or glucagon, C/EBPβ mRNA started to increase as early as at 30min, reached a maximum within 2h, and then gradually decreased. The administration of cycloheximide, a protein synthesis inhibitor, led rather to an increase in C/EBPβ mRNA, which suggested that a labile negative protein factor (s) is involved in regulation of the C/EBPβ mRNA level. Cyclohex-imide further augmented the increases in C/EBPβ mRNA by dexamethasone and/or glucagon. Therefore, C/EBPβ mRNA accumulation in response to these hormones is apparently independent of ongoing protein synthesis. The elevation of the C/EBPβ mRNA level by these hormones was accounted for by increases in the rate of transcription of the C/EBPβ gene, as deduced on nuclear run-on analysis. Gel mobility shift analysis revealed that the DNA-binding activity of C/EBPβ was increased cooperatively by dexamethasone and glucagon. These results suggest that the C/EBPβ gene is primarily induced by glucocorticoids and/or glucagon and that the accumulated C/EBPβ protein is then involved in secondary activation of target genes in response to these hormones in the liver.