Insulin-like growth factor-II increases plasma osteocalcin concentration in newborn lambs

The influence of GH, IGF-I and IGF-II on plasma 1,25-(OH)2D and osteocalcin (OC) concentrations was studied in four groups of five newborn lambs each. They received a single i.v. injection of either purified bovine GH (1 IU/mg 600 micrograms/kg body wt), synthetic human IGF-I (10 or 200 micrograms/kg body wt) or synthetic human IGF-II (10 micrograms/kg body wt). Five controls were injected the same volume (1 ml) of solvent. IGF-II, but not GH or IGF-I, induced a rapid (1.5 h) and sustained (up to 18 h) increase of serum osteocalcin. This effect of IGF-II on plasma OC concentration was not mediated by 1,25-(OH)2D, which increased in plasma only 18 h after IGF-II injection. These data suggest that IGF-II stimulates, the in vivo secretion of OC by osteoblasts through a mechanism independent of 1,25-(OH)2D. Further studies are necessary to elucidate the mechanism of IGF-II action on osteocalcin synthesis and to explain the late increase of plasma 1,25-(OH)2D after IGF-II injection.