REGULATION OF THE RAT CLASS-I ALCOHOL-DEHYDROGENASE GENE BY GROWTH-HORMONE

Growth hormone (GH) increases the transcription of the rat class I alcohol dehydrogenase (ADH) gene. Two transcription factors, the CCAAT/enhancer binding protein (C/EBP) and the liver activator protein (LAP), were previously shown to bind to the ADH promoter at nucleotide positions -11 to -22 relative to the start-site of transcription and to activate the ADH promoter in co-transfection experiments. In this study, exposure of cultured rat hepatocytes to GH (1 μg/ml) for 4 days increased LAP mRNA, but not C/EBP mRNA, in conjunction with an increase in ADH mRNA. GH, in transient transfection experiments of primary rat hepatocyte cultures, activated an ADH promoter-reporter gene construct containing the C/EBP binding site, but failed to activate a construct containing a 4-bp mutation at this site. These results suggest that the effect of GH in enhancing ADH promoter activity is mediated by LAP binding to the C/EBP site. © 1993 Academic Press.