Differential regulation of the expression of 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase and pyruvate kinase by cyclic adenosine 3′,5′-monophosphate in fetal and adult hepatocytes

Incubation of fetal hepatocytes from 21-day-old rats with permeant derivatives of cyclic AMP (cAMP) or glucagon, increased the mRNA levels of 6-phosphofructo-2-kinase/fructose 2,6-bisphosphatase (PFK-2/FBPase-2), L-pyruvate kinase (L-PK) and phosphoenolpyruvate carboxykinase (PEPCK). Contrary to this behavior, adult hepatocytes exhibited a decrease in the PFK-2/FBPase-2 and L-PK mRNA levels when incubated under equivalent experimental conditions. Dexamethasone also increased the PFK-2/FBPase-2 mRNA levels and costimulation of fetal hepatocytes with dexamethasone and a permeant analogue of cyclic AMP enhanced the levels of PFK-2/FBPase-2 mRNA, a situation opposite to that exhibited by adult hepatocytes. Treatment of the hepatocytes with transcriptional and translational inhibitors also produced differential responses in both types of cells. The PFK-2/FBPase-2 mRNA in fetal hepatocytes was more stable than in the adult cells. These results suggest that specific transcriptional factors and regulatory pathways differentially operate in fetal and adult hepatocytes in the control of the responses of carbohydrate metabolism to cAMP. © 1995 wiley-Liss, Inc.This work was supported by grants 9110229 and 9210267 from the Fondo de Investigaciones Sanitarias de la Seguridad Social, Spain.Peer Reviewe