Glucose and Amino Acids Interact with Hormones to Control Expression of Insulin-Like Growth Factor-I and Growth Hormone Receptor mRNA in Cultured Pig Hepatocytes

Abstract

Nutrients and hormones are major determinants of animal growth, but the mechanisms of how nutrients influence the growth process are still unclear. A primary pig hepatocyte culture system was used to investigate possible direct effects of glucose and individual amino acids on the expression of growth hormone receptor (GHR) and insulin-like growth factor-I (IGF-I) mRNA. The removal of glucose from the culture medium for 40 h resulted in significant reductions (to 45% of control, P = 0.013) in the expression of GHR in the presence of growth hormone (GH), dexamethasone (DEX) and tri-iodothyronine (T3). The decrease in GHR expression with removal of glucose from the culture medium resulted in a decreased response in class 1 (22% of control, P = 0.011) and 2 (5% of control P = 0.068) transcripts of IGF-I to any GH added. The effects of glucose on GHR and IGF-I expression were dose-dependent, appearing to plateau at ∼1–2 g/L (P = 0.031, for quadratic trend). Removal of arginine, proline, threonine, tryptophan or valine inhibited the stimulation of IGF-I expression that was induced by the combination of T3, DEX and GH (to 15, 6, 11, 16 and 16% of control, respectively, P < 0.05), with significant decreases in GHR expression also observed in some cases. The stimulatory effect of some of these amino acids (arginine, proline, threonine and tryptophan) was dose-dependent for expression of class 1 transcripts of IGF-I (P = 0.041, 0.022, 0.016 and 0.097, respectively, for linear trends), but there was no effect on GHR or class 2 transcripts of IGF-I. Whether the observed effects of nutrients on mRNA levels are due to direct effects on gene transcription or differences in mRNA stability remains to be established. Energy, in the form of glucose, appears to control GHR expression, interacting with the effects of glucocorticoids and thyroid hormones, whereas protein, in the form of certain individual amino acids, appears to control GH-stimulated IGF-I expression.