Studies on the roles of insulin-like growth factor-1 (IGF-1)/somatomedin C (SMC) during pregnancy

Abstract

Studies in human as well as animal experiments have proved that IGF-1/SMC, which shows mitogenic activities in a wide variety of cell types, stimulates growth in vitro and in vivo. The aim of this study was to investigate the roles of IGF-1/SMC on fetal growth during pregnancy by measuring IGF-1/SMC, insulin, C-peptide, human placental lactogen (hPL), and GH and PRL concentrations in maternal and fetal plasma, and by clarifying the changes of IGF receptor in human fetal liver microsomal membranes during pregnancy. Maternal plasma IGF-1/SMC concentrations were not distinguishable from those of nonpregnant women (9.2 +/- 1.7 nmol/l) in the 1st and 2nd trimester of gestation; however, they showed a gradual increase after the 30th week of gestation, reaching 12.7 +/- 5.4 at term. They possessed a significant positive correlation with hPL (r = 0.45, p less than 0.05) and PRL (r = 0.38, p less than 0.05) but not with GH (r = 0.39, NS). On the other hand, IGF-1/SMC in cord plasma could be first detected in the 30th week of gestation, and it increased gradually until term but had no significant correlation with that in maternal plasma. Furthermore, it possessed an intimate correlation with C-peptide (r = 0.30, p less than 0.05) but not with GH or PRL. Additionally, IGF-1/SMC in cord plasma had a positive correlation with birth weight (r = 0.60, p less than 0.005). On the other hand, specific binding of 125I-IGF-1 and -II to liver microsomal membranes which was also displaced by nonlabeled insulin could be detected in human fetuses at various gestational ages. Scatchard analyses indicated that the binding affinity, which was 0.14 +/- 0.05(x 10(9)M-1) in the fetal liver before the 19th week of gestation, increased after the 19th week of gestation (0.58 +/- 0.12); conversely, the binding capacity was lower after the 19th week of gestation (0.15 +/- 0.08 x 10(-12) moles/mg protein) compared with that before the 19th week (0.51 +/- 0.25). These results suggest that (1) plasma IGF-1/SMC might be produced in fetal sites and its regulating mechanism is different from that in maternal sites, and that (2) IGFs might play an important role in human fetal growth and development by its affect via IGF or insulin receptors on the human fetal liver.