Requirements of both glucocorticoids and glucagon as co-inducers for activation of transcription of the serine dehydratase gene in cultured rat hepatocytes

Abstract

Induction of translatable mRNA for serine dehydratase (SDH) in primary cultured rat hepatocytes requires both dexamethasone and glucagon or cAMP (Noda, C., Tomomura, M., Nakamura, T., and Ichihara, A. (1986) J. Biochem. (Tokyo) 95, 37-45). This unique hormone requirement was studied further with a cDNA probe complementary to SDH mRNA in primary cultured hepatocytes of adult rats. Dot-blot hybridization analysis of RNA showed that SDH mRNA was induced by dexamethasone and glucagon together, but not by either alone. Insulin or epinephrine caused 40% inhibition of this induction of SDH mRNA. Cycloheximide prevented the induction of SDH mRNA by dexamethasone and glucagon, suggesting that ongoing protein synthesis is required for the induction by glucocorticoids and glucagon. In vitro transcription experiments using nuclei isolated from cultured hepatocytes showed that transcription of the SDH gene was not affected by either dexamethasone or glucagon alone, but markedly enhanced by both hormones together, and that this enhancement was inhibited by insulin or epinephrine. These results indicate that the inhibition of SDH induction by epinephrine or insulin was due to effects of these hormones on the transcriptional rate of the SDH gene.