Regulation of tyrosine aminotransferase gene expression by glucocorticoids in quiescent and regenerating liver

Abstract

Following 70% hepatectomy, the induction of tyrosine aminotransferase mRNA by glucocorticoids was marginal at 1.5 h, significantly impaired between 3 and 8 h and, at 16 h post-hepatectomy, reached a value approx. 5-fold the basal level, similar to the level observed in quiescent liver. The fold induction of the mRNA was accounted for by a similar fold activation of transcription of the gene by glucocorticoids in regenerating but not in quiescent liver; in the latter, activation of transcription was marginal in spite of glucocorticoid-induced hypersensitivity to cleavage by DNase I at the glucocorticoid-dependent enhancer of the gene. The possibility that in quiescent liver glucocorticoids act at a transcriptional step beyond initiation, increasing the rate of elongation or overcoming a blockage in elongation, was excluded. However, a similar fold induction was determined for total and nuclear tyrosine aminotransferase mRNA in the presence of glucocorticoids, suggesting that in quiescent liver glucocorticoids promote efficient maturation of the tyrosine aminotransferase primary transcript. Thus a glucocorticoid-induced nuclear post-transcriptional up-regulation apparently compensates for impaired activation of transcription of the tyrosine aminotransferase gene by glucocorticoids in quiescent liver.