The free form of insulin-like growth factor I increases in circulation during normal human pregnancy

The main circulating insulin-like growth factor-binding protein (IGFBP) in human, IGFBP-3, markedly decreases during pregnancy, as determined by Western ligand blotting, and its decrease is due to an endogenous pregnancy-related serum IGFBP-3 proteolytic activity. Proteolysis of IGFBP-3 may result in the free form of IGF-I (fIGF-I) being liberated from or weakly bound to IGFBP-3 fragments. The purpose of this study was to determine the plasma concentration of fIGF-I and the mechanism of fIGF-I regulation during normal human pregnancy. We studied 19 normal pregnant women at 6-8 weeks gestation, 24 normal pregnant women at 28-30 weeks gestation, and 25 nonpregnant women. We measured plasma fIGF-I using a recently established immunoradiometric assay. We also measured plasma total IGF-I (free plus complexed forms of IGF-I) using immunoradiometric assay, and IGFBP-3 proteolytic activity using a IGFBP-3 protease assay. fIGF-I levels at 6-8 weeks gestation (4.11 +/- 0.23 ng/mL) and at 28-30 weeks gestation (3.67 +/- 0.21 ng/mL) were significantly higher than that in nonpregnant women (2.48 +/- 0.12 ng/mL; P < 0.001 in both). Total IGF-I levels at 6-8 weeks gestation (168.0 +/- 9.1 ng/mL) and at 28-30 weeks gestation (241.5 +/- 19.0 ng/mL) were significantly lower than that in nonpregnant women (283.9 +/- 12.3 ng/mL; P < 0.001 at 6-8 weeks gestation and P < 0.05 at 28-30 weeks gestation). All pregnant serum studied had IGFBP-3 proteolytic activity. These data indicate that during normal human pregnancy, circulatory fIGF-I increases, probably due to IGFBP-3 proteolytic activity.