The Ontogeny and Regulation of a 31,000 Molecular Weight Insulin-Like Growth Factor-Binding Protein in Fetal Porcine Plasma and Sera*

Studies were conducted to determine the presence, quantity, and regulation of insulin-like growth factor (IGF)-binding proteins in porcine plasma and sera. The size distribution of IGF-binding protein was determined by affinity cross-linking to 125IIGF-I, and the binding activity was quantified by a polyethylene glycol precipitation procedure. The major 125IIGF-I-binding protein complex was of 38,000 mol wt (Mr) in all porcine sera or plasma tested. Binding to this protein was inhibited by excess unlabeled IGF-I, but not by insulin. When plasma samples from fetuses at 45, 70, 90, and 110 days gestation were cross-linked to 125IIGF-I, there was an increase in the concentration of the 38,000 Mr complex with advancing gestational age, whereas plasma from the mothers of the age-matched fetuses showed little change in the amount of the 38,000 Mr complex. When the binding activity of the fetal plasma was quantified, there was a significant increase in binding activity between 45 and 110 days gestation from 30.5 +/- 3.3% to 77.5 +/- 3.6% (+/- SE) of the assay maximum. This increase was not due to a decrease in binding protein saturation, since the endogenous IGF-I levels (quantified after acid gel filtration chromatography) also increased with advancing gestational age, from 176 to 458 mU/ml. Blood samples were collected from porcine fetuses at 110 days gestation that had either been decapitated or spinal cauterized at 45 days gestation. Decapitation decreased the amount of the 38,000 Mr complex that could be detected by affinity labeling. In contrast, spinal cauterization had no effect on the amount of the 38,000 Mr complex in fetal plasma compared to that in control fetal plasma. These results were verified in the polyethylene glycol assay. These studies show that the amount of the 38,000 Mr IGF-binding protein complex in pig plasma is developmentally regulated and suggest that a pituitary or neural factor may be an important variable in the control of its plasma concentrations.