Direct effects of growth hormone on production and secretion of apolipoprotein B from rat hepatocytes

The aim of this study was to investigate the direct effects of growth hormo ne (GH) on production and secretion of apolipoprotein B (apoB)-containing l ipoproteins from hepatocytes. Bovine GH (5-500 ng/ml) was given for 1 or 3 days to rat hepatocytes cultured on laminin-rich matrigel in serum-free med ium. The effects of GH were compared with those of 3 nM insulin and 500 muM oleic acid. GH increased the editing of apoB mRNA, and the proportion of n ewly synthesized apoB-48 (of total apoB) in the cells and secreted into the medium changed in parallel. GH increased total secretion of apoB-48 (+30%) and apoB-48 in very low density lipoproteins (VLDL) more than twofold. Tot al apoB-100 secretion decreased 63%, but apoB-100-VLDL secretion was unaffe cted by GH. Pulse-chase studies indicated that GH increased intracellular e arly degradation of apoB-100 but not apoB-48. GH had no effect on apoB mRNA or LDL receptor mRNA levels. The triglyceride synthesis, the mass of trigl ycerides in the cells, and the VLDL fraction of the medium increased after GH incubation. Three days of insulin incubation had effects similar to thos e of GH. Combined incubation with oleic acid and GH had additive effects on apoB mRNA editing and apoB-48-VLDL secretion. In summary, GH has direct ef fects on production and secretion of apoB-containing lipoproteins, which ma y add to the effects of hyperinsulinemia and increased flux of fatty acids to the liver during GH treatment in vivo.