PIERCE, A.L.; SHIMIZU, M.; DICKHOFF, W.W.; Univ Washington, Seatte; Univ Washington, Seattle; NOAA-Fisheries: EFFECTS OF METABOLIC HORMONES ON INSULIN-LIKE GROWTH FACTOR BINDING PROTEIN-1 (IGFBP-1) MESSENGER RNA LEVEL IN PRIMARY CULTURED SALMON HEPATOCYTES

Insulin-like growth factor (IGF) binding proteins (IGFBPs) modulate the effects of the IGFs, major stimulators of vertebrate growth and development. Work in mammals has shown that hepatic production of IGFBP-1 increases rapidly during fasting, stress, and in other catabolic states, and that IGFBP-1 is generally growth inhibitory. A low molecular weight (22 kDa) IGFBP in salmon and other fish blood shows similar regulation. The salmon IGFBP-1 cDNA has recently been cloned and identified as corresponding to the circulating 22 kDa IGFBP. We developed a TaqMan quantitative PCR assay for salmon IGFBP-1 mRNA, and examined the hormonal regulation of IGFBP-1 mRNA level in primary cultured salmon hepatocytes. Dexamethasone (Dex) and glucagon increased hepatocyte IGFBP-1 mRNA levels. Dex concentrations approximating circulating cortisol under stressed conditions strongly induced IGFBP-1 (10^-9 to 10^-7 M; 8.1 fold increase), whereas glucagon was only effective at pharmacological concentrations (10^-6 M; 2.2 fold increase). Growth hormone (GH) progressively reduced IGFBP-1 mRNA levels at physiological concentrations and above (5 x 10^-9 to 2.5 x 10^-7 M; 3.1 fold decrease). Surprisingly, insulin did not change or slightly increased hepatocyte IGFBP-1 mRNA levels at physiological concentrations (10^-8 and 10^-7 M; 1.4 fold increase). Triiodothyronine did not affect IGFBP-1 mRNA levels. This study shows that regulation of IGFBP-1 by Dex, glucagon, and GH in salmon hepatocytes is similar to mammals. However, insulin strongly inhibits liver IGFBP-1 gene expression and reduces circulating protein levels in mammals, suggesting that insulin regulation of IGFBP-1 differs between fishes and mammals. (Supported by NRI-CSREES USDA-2003-03314.)