Multihormonal regulation of 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase gene expression in primary cultures of rat hepatocytes

In the absence of hormone, 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase mRNA rapidly declined to undetectable levels in primary cultures of rat hepatocytes. Dexamethasone increased mRNA levels and this effect was blocked by actinomycin D or cycloheximide. Insulin or thyroxine had no effect but potentiated the dexamethasone induction. Dibutyryl cyclic AMP decreased the stimulatory effect of dexamethasone at early times but after 24 hours the cyclic nucleotide increased mRNA levels compared with dexamethasone alone. It was concluded that expression of the bifunctional enzyme gene in hepatocytes is under a complex multihormonal control. Glucocorticoids are the most important transcriptional factor and their effect requires ongoing protein synthesis.