ABSTRACT. The metabolic consequences of a prolonged gestation (35 vs 32 days) have been studied in the rabbit fetus. Gestation was prolonged by daily subcutaneous injections of progesterone (1.5 mg-kg-') from day 28 to 34. In control animals, progesterone was injected from day 25 or 28 to day 31 of gestation. When the capacities for gluconeogenesis and fatty acid oxidation, measured on isolated hepatocytes, are normally low in the term control fetus and increase only within the first 24 h after birth, these capacities appear high in the postmature fetus. The rate of glucose production from lactate is 4-fold higher in the postmature fetus than in the normal term fetus. The rate of ketone body production from oleate is also 5-fold higher in the postmature fetus, which results from a switch on of the partition of oleate into esterification and oxidation: 8% of [1-14Cjoleate is oxidized in term fetus hepatocytes, but 34% in postmature fetus hepatocytes. As a similar rate of lipogenesis takes place in both stages, this metabolic change could be explained by a 5-fold lower sensitivity of carnitine palmitoyltransferase I to the inhibition by malonyl-coenzyme A. Postmaturity decreases plasma insulin concentrations by 45% and increases plasma glucagon concentrations by 50% which, in turn, induces a 3-fold decrease in the plasma insu1in:glucagon molar ratio. As previously shown in fasted or diabetic adult rat, this hormonal change might be a likely candidate for an enhancement of gluconeogenic and ketogenic capacity in the liver of the postterm rabbit fetus. (Pediatr Res 23: 224-228,1988) Abbreviation CoA, coenzyme A During pregnancy, the fetus receives a continuous supply of nutrients, principally glucose and amino acids for its growth and its oxidative metabolism which makes unnecessary the development of metabolic pathways as those involved in endogenous glucose production or free fatty acid oxidation (1). Previous studies performed in rabbit hepatocytes have shown that gluconeogenesis from lactate or oleate oxidation and ketogenesis proceed to a very low rate in term fetus and increase during the first day after birth (2, 3). The postnatal emergence of hepatic gluconeogenesis and fatty acid oxidation correspond to a shifting of Received July 31, 1987; accepted October 14, 1987. Correspondence and reprint requests Pierre-Henri Duk, Centre de Recherches sur la Nutrition, CNRS, 9 rue Jules Hetzel, 92 190 Meudon-Bellevue, France.Supported in part by Grant CRE 867010 from the Institut National de la Santt et de la Recherche MCdicale. specific limiting steps that have been well described. The emergence of hepatic gluconeogenesis in the newborn rabbit may result from a rapid fall in hepatic fructose 2,6-bisphosphate concentration (4) and from an increase in the activity of cytosolic phosphoenolpyruvate carboxykinase (2). Moreover, it has been shown that the postnatal increase in mitochondria1 adenine nucleotide content stimulates pyruvate carboxylation causing a rapid increase in the rate of hepatic gluconeogenesis (5,...
