Effects of maternal nutrient restriction, intrauterine growth restriction, and glucocorticoid exposure on phosphoenolpyruvate carboxykinase-1 expression in fetal baboon hepatocytes in vitro

J Med Primatol. 2013 Aug;42(4):211-9. doi: 10.1111/jmp.12048. Epub 2013 Apr 20.

Abstract

Background: The objective of this study was to develop a cell culture system for fetal baboon hepatocytes and to test the hypotheses that (i) expression of the gluconeogenic enzyme phosphoenolpyruvate carboxykinase-1 (PEPCK-1) is upregulated in hepatocytes isolated from fetuses of nutrient-restricted mothers (MNR) compared with ad libitum-fed controls (CTR), and (ii) glucocorticoids stimulate PEPCK-1 expression.

Methods: Hepatocytes from 0.9G CTR and MNR fetuses were isolated and cultured. PEPCK-1 protein and mRNA levels in hepatocytes were determined by Western blot and quantitative PCR, respectively.

Results: Fetuses of MNR mothers were intrauterine growth restricted (IUGR). Feasibility of culturing 0.9G fetal baboon hepatocytes was demonstrated. PEPCK-1 protein levels were increased in hepatocytes isolated from IUGR fetuses, and PEPCK-1 mRNA expression was stimulated by glucocorticoids in fetal hepatocytes.

Conclusions: Cultured fetal baboon hepatocytes that retain their in vivo phenotype provide powerful in vitro tools to investigate mechanisms that regulate normal and programmed hepatic function.

Keywords: dexamethasone; diabetes non-human primate; liver.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cells, Cultured
  • Dexamethasone / administration & dosage
  • Female
  • Fetal Growth Retardation / enzymology*
  • Food Deprivation*
  • Gene Expression / drug effects
  • Glucocorticoids / administration & dosage*
  • Hepatocytes / enzymology*
  • Liver / embryology
  • Liver / enzymology
  • Male
  • Maternal-Fetal Exchange
  • Papio / embryology*
  • Phosphoenolpyruvate Carboxykinase (GTP) / analysis
  • Phosphoenolpyruvate Carboxykinase (GTP) / genetics*
  • Pregnancy
  • RNA, Messenger / analysis

Substances

  • Glucocorticoids
  • RNA, Messenger
  • Dexamethasone
  • Phosphoenolpyruvate Carboxykinase (GTP)