title: Role of glucocorticoids in activation of hepatic PEPCK gene transcription during exercise.
abstract: The objective of these studies was to determine the molecular basis for the activation of phosphoenolpyruvate carboxykinase (PEPCK) gene transcription during prolonged submaximal exercise. Mice were fed a high-carbohydrate diet for 1 wk and exercised continuously by swimming for up to 120 min. The level of hepatic PEPCK mRNA increased progressively during exercise, reaching 510% above control, whereas transcription of the PEPCK gene increased 1,000%, before decreasing to control levels within 60 min of recovery. In transgenic mice carrying a chimeric gene consisting of the PEPCK promoter linked to a reporter gene for bovine growth hormone (bGH), PEPCK(-460)-bGH, the level of hepatic bGH mRNA increased by 490% in response to exercise, similar to the increase in the expression of the native PEPCK gene. However, in transgenic mice with a deletion of the glucocorticoid regulatory unit, PEPCK(-355)-bGH, bGH mRNA did not increase above control values. In transgenic mice with a block mutation in adenosine 3',5'-cyclic monophosphate (cAMP) regulatory regions -90/-82 and -250/-234, PEPCK cAMP response element 1 (CRE-1)/P3(1)-bGH, exercise increased bGH mRNA 260% above controls. Adrenalectomy (Adx) had no effect on PEPCK mRNA levels in nonexercised mice, whereas in adrenalectomized (Adx)-exercised mice, PEPCK mRNA increased only 80% above basal, and, in Adx mice injected with dexamethasone, PEPCK mRNA increased with exercise 570% above controls. Exercise was also associated with a large increase in transcription of the gene for the transcription factor CCAAT/enhancer-binding protein beta (C/EBP-beta) and a smaller rise in transcription of c-jun gene, both of which returned to control levels during recovery.(ABSTRACT TRUNCATED AT 250 WORDS)
authors.affiliation: Pew Center for Molecular Nutrition, Case Western Reserve University School of Medicine, Cleveland, Ohio 44106-4935.
authors.forename: J E
authors.initials: JE
authors.lastname: Friedman
mesh_terms: D000818:Animals; D022762:CCAAT-Enhancer-Binding Proteins; D004268:DNA-Binding Proteins / Q000235:genetics; D005938:Glucocorticoids / Q000502:physiology*; D008099:Liver / Q000201:enzymology*; D051379:Mice; D008810:Mice, Inbred C57BL; D009687:Nuclear Proteins / Q000235:genetics; D010729:Phosphoenolpyruvate Carboxykinase (GTP) / Q000235:genetics*; D005082:Physical Exertion; D012333:RNA, Messenger / Q000378:metabolism; D014158:Transcription, Genetic
chemical_list: D022762:CCAAT-Enhancer-Binding Proteins; D004268:DNA-Binding Proteins; D005938:Glucocorticoids; D009687:Nuclear Proteins; D012333:RNA, Messenger; D010729:Phosphoenolpyruvate Carboxykinase (GTP)