Transcription activation of the tyrosine aminotransferase gene by glucocorticoids and cAMP in primary hepatocytes

Abstract

The expression of the tyrosine aminotransferase (TAT) gene of the rat was analyzed in primary hepatocytes. The TAT gene remains active in primary cultured cells at a level similar to that in liver cells. Expression can be induced by glucocorticoids and cAMP, glucocorticoids lead to a 8-10-fold increase in TAT mRNA level, cAMP to a 20-30-fold increase. The elevation of the TAT mRNA is preceeded by a rise in the relative rate of transcription of the gene. Surprisingly transcription of the albumin gene, which steadily declines with the age of the culture, can also strongly be stimulated by glucocorticoids in primary hepatocytes. cAMP antagonists, which act as competitive inhibitors of the cAMP-dependent protein kinase, prevent induction of transcription of the tyrosine aminotransferase gene by cAMP suggesting that the effect of cAMP on expression of the tyrosine aminotransferase gene is mediated by a cAMP-dependent protein kinase. The cAMP antagonist does not interfere with induction by glucocorticoids which suggests that phosphorylation of the glucocorticoid receptor by the cAMP-dependent protein kinase is not required for its function. We thus conclude that the two inducers affect transcription by independent mechanisms.