Insulin‐like growth factor II binding and action in human fetal fibroblasts

Abstract

To investigate the role of insulin‐like growth factor II (IGF‐II) in human prenatal growth, IGF‐II binding and biological action were studied in four lines of fetal and three lines of postnatal human fibroblasts. Specific biniding of IGF‐II was similar in both groups: 15.7% and 14.9% for fetal and postnatal fibroblasts, respectively. This was 5–10 times the amount of IGF‐I binding found in these cells. IGF‐I and IGF‐II caused dose‐dependent increases in [¹⁴C]aminoisobutyric acid (AIB) uptake. IGF‐II was sevenfold less potent than IGF‐I in stimulating this metabolic response in both fetal and postnatal fibroblasts. The maximal effect of IGF‐II in stimulating [¹⁴C]AIB uptake approached that of IGF‐I. Similar results were obtained when IGF‐I and IGF‐II stimulation of [³H]thymidine incorporation was compared in fetal and postnatal fibroblasts. Incubation in the presence of alphalR‐3, a monoclonal antibody to the type I IGF receptor, inhibited the ability of both IGF‐I and IGF‐II to stimulate [¹⁴C]AIB uptake and [³H]thymidine incorporation in fetal and postnatal cells. A monoclonal antibody to the insulin receptor did not affect IGF action. These data indicate that IGF‐II is a potent metabolic and mitogenic stimulus for human fetal firoblasts. However, despite the presence of abundant type II IGF receptors on both fetal and postnatal human fibroblasts, IGF‐II stimulation of amino acid transport and DNA synthesis appears to be mediated through the type I rather than through its own type II IGF receptor.