DEVELOPMENTAL REGULATION OF BASAL AND HORMONE-INDUCIBLE PHOSPHOENOLPYRUVATE CARBOXYKINASE GENE-EXPRESSION IN CHICK-EMBRYO LIVER IN-VIVO

We have examined cytosolic phosphoenolpyruvate carboxykinase (PEPCK, E C 4.1.1.32) gene transcription and steady-state mRNA expression in chi ck embryo liver in vivo both constitutively and in response to dexamet hasone, cAMP, retinoic acid, and the protein synthesis inhibitors, cyc loheximide and pactamycin. We report here that PEPCK mRNA is constitut ively expressed between 12 and 16 days of development. PEPCK expressio n was also transiently but highly inducible on Day 14 by dexamethasone , cAMP, cycloheximide, and pactamycin, but not by retinoic acid. Cyclo heximide pretreatment had an additive or synergistic effect on the ind uction by dexamethasone and/or cAMP. Dexamethasone- and cycloheximide- induced increases in mRNA expression were principally due to increases in the rate of PEPCK gene transcription. Following an initial inducti on by dexamethasone, PEPCK expression was no longer responsive to a se cond administration of dexamethasone but was still responsive to cyclo heximide and cAMP. PEPCK induction by dexamethasone or cycloheximide p rogressively diminished between 12 and 15 days of development. By Day 16, PEPCK expression was no longer responsive to dexamethasone, but wa s still inducible by cAMP and this induction was increased by cyclohex imide. These results indicate that PEPCK is transiently inducible by g lucocorticoids in chick embryo liver and that there are two developmen tal switches to the adult phenotype between Days 14 and 16 of developm ent and between Day 16 and 4 days posthatching. Our results also sugge st the presence of a developmentally regulated repressor of PEPCK gene expression in chick embryo liver. (C) 1994 Academic Press, Inc.