Glucocorticoid regulation of hepatic 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase gene expression

The effect of adrenalectomy and triamcinolone treatment on mRNA encoding rat hepatic 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase was studied. Adrenalectomy decreased both the kinase and the bisphosphatase activities of the bifunctional enzyme to about 30% of the values in livers of normal rats. Triamcinolone treatment restored both activities to normal by 24 h. These changes were caused by alterations in the concentration of the enzyme as determined by immunoblotting and by an assay that measures phosphoenzyme formation. Messenger RNA for liver 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase was markedly decreased by adrenalectomy and was increased 15-fold by triamcinolone administration for 8 h. The rate of transcription of the bifunctional enzyme gene, measured in rat liver nuclei, was also decreased in adrenalectomy, and triamcinolone treatment increased this rate 5-fold within 8 h. Similarly, liver nuclear precursors of 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase mRNA were decreased by adrenalectomy to 25% of the level in nuclei from normal rats. Triamcinolone treatment restored heterogeneous nuclear RNA of the bifunctional enzyme to control values by 2 h, while treatment for 30 h increased it 12-fold over the adrenalectomized levels. It was concluded that glucocorticoids regulate the expression of 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase, at least in part, by modulating the transcription rate of the gene.