Effect of STAT5b on Rat Liver Alcohol Dehydrogenase

Growth hormone (GH) enhances rat liver alcohol dehydrogenase (ADH) due to an increase in enzyme synthesis, which is mediated at the level of transcription. Previous studies have shown that the effect of GH in enhancing activation of the ADH promoter is mediated by C/EBPβ binding to region −22 to −11 relative to the start of transcription. In this study, STAT5b and C/EBPβ were found to bind to adjacent nucleotide sequences on a region between −226 and −194. Expression vectors for both STAT5b and C/EBPβ independently activated the promoter. Furthermore, the expression vector for the GH receptor also activated the ADH promoter, and this effect was abrogated by mutations of the adjacent STAT5b and C/EBPβ binding sites. These observations indicate that the enhancing effect of GH is mediated by both STAT5b and C/EBPβ.