Insulin-like growth factor II binding and action in human fetal fibroblasts.
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 binding 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 approach 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 alpha IR-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 fibroblasts. 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.
D000621:Aminoisobutyric Acids / Q000378:metabolism; D000911:Antibodies, Monoclonal / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D005314:Embryonic and Fetal Development; D005333:Fetus / Q000378:metabolism* / Q000502:physiology; D005347:Fibroblasts / Q000378:metabolism* / Q000502:physiology; D006801:Humans; D007328:Insulin / Q000378:metabolism; D007334:Insulin-Like Growth Factor I / Q000378:metabolism / Q000494:pharmacology; D007335:Insulin-Like Growth Factor II / Q000378:metabolism* / Q000494:pharmacology / Q000502:physiology; D011972:Receptor, Insulin / Q000276:immunology; D017451:Receptors, Somatomedin; D013002:Somatomedins / Q000378:metabolism*; D013268:Stimulation, Chemical; D013936:Thymidine / Q000378:metabolism
D000621:Aminoisobutyric Acids; D000911:Antibodies, Monoclonal; D007328:Insulin; D017451:Receptors, Somatomedin; D013002:Somatomedins; D007334:Insulin-Like Growth Factor I; D007335:Insulin-Like Growth Factor II; D011972:Receptor, Insulin; D013936:Thymidine