ONTOGENY OF INSULIN-LIKE GROWTH-FACTORS (IGF-I AND IGF-II) AND IGF-BINDING PROTEINS IN PORCINE SERUM DURING FETAL AND POSTNATAL-DEVELOPMENT

The insulin-like growth factors (IGF-I and IGF-II) circulate in plasma in association with IGF-binding proteins (IGFBPs). As a first step to understanding the regulation of expression of these proteins in pigs, we characterized the ontogeny of circulating IGFs and IGFBPs during fetal and early postnatal development. Serum IGFs were separated from IGFBPs, before IGF RIA, by acidification and chromatography on C18 Sep-Pak cartridges. The IGF-I levels increased during the latter half of fetal life from 11 +/- 1 ng/ml on day 60 to 37 +/- 3 ng/ml on day 112(2-3 days before term) and further increased postnatally to 227 +/- 22 ng/ml on day 42. IGF-II levels were higher than IGF-I levels, with no obvious developmental pattern, during fetal life (170 +/- 21 to 265 +/- 26 ng/ml) and also increased postnatally by 2-fold (463 +/- 29 ng/ml on day 42). These results support the view that IGF-II is a fetal and postnatal growth factor, whereas IGF-I is primarily a postnatal growth mediator in pigs. Serum IGF-binding proteins were identified by Western ligand blotting. Five IGFBPs with apparent mol wt of 43K, 39K, 34K, 31K, and 26K were detected in fetal and postnatal sera. The two largest proteins were shown to be glycoproteins and immunologically related to porcine (p) IGFBP-3, suggesting that they are glycosylation variants of pIGFBP-3. The abundance of these two IGFBPs increased coincidentally with increasing serum IGF-I levels. The 34K IGFBP was immunologically related to rIGFBP-2 and was 2- to 3-fold more abundant in fetal serum than in postnatal serum. The 31K IGFBP was resolved into a triplet and also was a component of pIGFBP-3 immunoprecipitates. Similarly, the 26K IGFBP was present in pIGFBP-3 immunoprecipitates. The 31K and 26K IGFBPs represented a minor portion of serum IGF-binding activity in fetal and postnatal pigs and exhibited no obvious developmental patterns. It is hypothesized that the postnatal increases in serum IGF-I and 43K and 39K IGFBPs as well as the decrease in the 34K IGFBP are driven by GH action.