Ontogeny of Receptors for Insulin-Like Peptides in Chick Embryo Tissues: Early Dominance of Insulin-Like Growth Factor over Insulin Receptors in Brain*

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Abstract
Recently, we confirmed early data showing deleterious effects of exogenous insulin on chick embryos at 2 days of development, although insulin receptors were not clearly demonstrable until days 3-4. Now we report that insulin-like growth factor (IGF) receptors are present in whole embryos on day 2. The developmental patterns of [125I]IGF-I and [125I]IGF-II binding to brain were similar, and IGF-I showed approximately a 2-fold higher binding than IGF-II; there was a sharp increase from days 3 to 6, and a subsequent gradual fall during the second and third weeks of ontogeny. Competitive binding experiments with unlabeled analogs suggested that both labeled IGFs were binding to type II GF receptors, and insulin interacted with them. The temperature and pH dependence were relatively higher than those for some other known IGF receptors. We have previously reported that [125I]insulin binding to brain is barely detectable on day 3 and shows a progressive rise throughout the rest of embryonic life. The pattern of IGF and insulin receptors appears to be organ specific, since nonneural tissues such as heart, liver, and limb buds showed different binding profiles in ontogeny. We conclude from these data that IGF receptors develop in chick embryo brain before insulin receptors and probably can mediate effects of IGF and insulin at early stages of embryogenesis.