Induction of glutamate dehydrogenase in the ovine fetal liver by dexamethasone infusion during late gestation
Glucocorticoids near term are known to upregulate many important enzyme systems prior to birth. Glutamate dehydrogenase (GDH) is a mitochondrial enzyme that catalyzes both the reversible conversion of ammonium nitrogen into organic nitrogen (glutamate production) and the oxidative deamination of glutamate resulting in 2-oxoglutarate. The activity of this enzyme is considered to be of major importance in the development of catabolic conditions leading to gluconeogenesis prior to birth. Ovine hepatic GDH mRNA expression and activity were determined in near-term (130 days of gestation, term 147 +/- 4 days) control and acutely dexamethasone-treated (0.07 mg(-1) hr(-1) for 26 hr) fetuses. Dexamethasone infusion had no effect on placental or fetal liver weights. Dexamethasone infusion for 26 hr significantly increased hepatic GDH mRNA expression. This increased GDH mRNA expression was accompanied by an increase in hepatic mitochondrial GDH activity, from 30.0 +/- 7.4 to 58.2 +/- 8.1 U GDH/U CS (citrate synthase), and there was a significant correlation between GDH mRNA expression and GDH activity. The generated ovine GDH sequence displayed significant similarity with published human, rat, and murine GDH sequence. These data are consistent with the in vivo studies that have shown a redirection of glutamine carbon away from net hepatic glutamate release and into the citric acid cycle through the forward reaction catalyzed by GDH, i.e., glutamate to oxoglutarate.
|Animals, Base Sequence, DNA, Complementary, Dexamethasone/administration & dosage/*pharmacology, Enzyme Induction, Female, Glutamate Dehydrogenase/*biosynthesis/genetics, Liver/*drug effects/embryology/enzymology, Molecular Sequence Data, Pregnancy, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S., Reverse Transcriptase Polymerase Chain Reaction, Sequence Homology, Nucleic Acid, Sheep/*embryology|
|Experimental Biology and Medicine|
|Organisation||Erasmus MC: University Medical Center Rotterdam|
Timmerman, M, Wilkening, R.B, & Regnault, T.R. (2003). Induction of glutamate dehydrogenase in the ovine fetal liver by dexamethasone infusion during late gestation. Experimental Biology and Medicine. Retrieved from http://hdl.handle.net/1765/10053