PIERCE, A.L.; FUKADA, H.; DICKHOFF, W.W.; Univ Washington; Univ Washington; Univ Washington: Metabolic hormones modulate the effect of growth hormone (GH) on insulin-like growth factor-I (IGF-I) expression in primary culture of salmon hepatocytes

Liver production of IGF-I is a major point of control in the growth axis, the main endocrine system regulating body growth in fishes and other vertebrates. Pituitary GH stimulates hepatic production of IGF-I; however, in catabolic states hepatic GH resistance results in decreased liver IGF-I production. To investigate endocrine mechanisms leading to the development of GH resistance, we examined the regulation of IGF-I mRNA level by GH and metabolic hormones in primary culture of salmon hepatocytes. Cells were cultured in RPMI medium, and exposed to insulin (Ins, 1 μM), glucagon (Glu, 1 μM), triiodothyronine (100 nM), dexamethasone (Dex, 1 μM), and glucagon-like peptide (1 μM) in the presence and absence of GH (5 nM). GH always increased IGF-I mRNA. None of the other hormones tested affected IGF-I mRNA by itself. However, Dex, Ins, and Glu reduced the response to GH. The response to GH was inhibited by Dex at concentrations of 1 pM and above, by Ins at 1 nM and above, and by Glu only at 1 μM. Inhibition of GH response by glucocorticoids such as Dex is also found in mammals, and is consistent with the inhibitory effect of stress on growth. However, the inhibition of GH response by Ins in salmon hepatocytes is the inverse of what is found in tetrapods. To examine mechanisms for modulation of the effect of GH by metabolic hormones, we measured hepatocyte GH receptor (GHR) mRNA levels. Ins inhibited and Dex stimulated GHR mRNA, suggesting that different mechanisms mediate the inhibition of GH response by Ins and Dex. (Supported by NRI-CSREES USDA-2003-03314.)