Insulin-like Growth Factor (IGF) Receptor in Human Fetal Erythrocytes and Fetal Rat Liver

Abstract

In order to clarify the potential role of IGF-I in fetal growth, the dynamics of IGF receptor were investigated in comparison with insulin receptor in human and rat fetuses. In humans, the serum levels of IGF-I measured by IGF-I radioimmunoassay after acid-ethanol extraction were significantly lower in fetuses than in adult controls. Conversely, serum insulin levels in fetuses were not indistinguishable from those in adults. On the other hand, specific binding of 125I-IGF-I to human fetal erythrocytes was 2.3%, which was significantly higher than that of adult women (1.6%). Insulin binding to the erythrocytes was also higher in human fetuses than in adult controls (cord: 3.8%, adult: 3.0%). By Scatchard analysis, the changes in the specific binding of IGF-I and insulin were mainly due to the changes in the binding capacity rather than those in the binding affinity. Additionally, IGF receptor on human fetal erythrocytes was recognized as type I IGF receptor, because the binding of 125I-labelled IGF-I and 125I-labelled IGF-II could be displaced by the addition of cold IGF-I, IGF-II and insulin. In rats, serum levels of IGF-I were also much lower in fetuses than in adult controls. Specific binding of 125I-IGF-I to liver microsomal membranes was 34.3% (per 400 micrograms protein) in fetal rats (D20), which was significantly higher than that of adult rats (3.2%). Scatchard analysis indicated that these changes in 125I-IGF-I binding was chiefly due to the changes in binding capacity. On the other hand, serum insulin levels increased with progress of pregnancy, and specific binding of insulin to microsomal membranes of fetal liver increased on D21 of gestation, mainly due to the increase in binding affinity rather than binding capacity. The bindings of 125I-labelled IGF-I and 125I-labelled IGF-II to fetal liver microsomal membranes were clearly displaced by cold IGF-I and IGF-II but not by excess of cold insulin, indicating that the receptor was type 2 IGF receptor. These results suggest that IGF-I possesses much more receptor in fetal tissues than in adult tissues despite its lower concentration in fetal sera. It is speculated that IGF-I may play an important role in fetal growth and development.