Effect of GH status on IGF-I and IGF-II concentrations and serum IGF binding profiles in pigs

The present study was conducted to determine 1) whether porcine growth hormone (pGH) affected insulin-like growth factor (IGF)-II concentrations in growing pigs and 2) the distribution of [125I]IGF-I and [125I]IGF-II binding activity and immunoreactive IGF-I and IGF-II in serum from control, pGH-treated and hypophysectomized (hypox) pigs. Seven weeks of pGH treatment had no effect on serum IGF-II concentrations, but after 11 wk serum IGF-II had increased by up to 50%. In normal pig serum, [125I]IGF-I bound to specific insulin-like growth factor binding proteins (IGF-BP) of 40 kDa (87.5%) and 150 kDa (12.5%). Treatment with pGH increased the proportion of IGF-I bound to the large IGF-BP (approximately 48%). In contrast, [125I]IGF-II partitioned to specific IGF-BP of 450 kDa (30%), 150 kDa (46%) and 40 kDa (23%). After treatment with pGH, binding of IGF-II to the 150-kDa IGF-BP increased to 57% of total specific binding. Binding of IGF-I and IGF-II to the 150-kDa IGF-BP was virtually abolished in hypox pig serum. IGF-I immunoreactivity was predominantly associated with the 150-kDa IGF-BP (67 to 83%), with the remainder bound to the small IGF-BP. There was no detectable free IGF-I in pig serum. Treatment with pGH did not affect the distribution of immunoreactive IGF-I between the two IGF-BP complexes, although there was a marked elevation in total serum IGF-I concentration. Immunoreactive IGF-II was detected in all three IGF-BP complexes. In control serum, the largest quantity (46%) of immunoreactive IGF-II was associated with the 40-kDa IGF-BP. Thirty-four percent was bound to the 150-kDa IGF-BP complex. Administration of pGH led to an increased association with the 150-kDa complex (50%) and a concomitant decrease in IGF-II associated with the 40-kDa species (35%). In summary, IGF-II concentrations in the pig are elevated by prolonged pGH treatment. Furthermore, there is a unique large IGF-BP in postnatal pig serum that specifically binds IGF-II but not IGF-I.