SUBSTRATE AND ENDOCRINE INFLUENCES ON DEVELOPING LUNG

围产期生物学中的一个中心问题是底物 为胎儿的整体生长和特殊功能的发育提供营养 例如肺中表面活性剂合成。 我们将定义 底物利用率和生长因子对生物化学和 肺的形态成熟，并测试假设， 供应具有重要的成熟影响，可能通过 生长因子与细胞表面受体的相互作用。 这些研究最初将集中在表皮生长因子上。 两 将使用实验模型： 胎儿发育迟缓，IUGR的胎儿发育加速， 成熟 我们将描述EGF与细胞表面受体的结合， 糖尿病和IUGR妊娠。 这将包括调查 EGF结合在实验胎儿中的个体发育及其作用 胰岛素逆转糖尿病状态的受体数量和亲和力。 将进行免疫细胞化学研究以定位EGF 特定细胞类型的受体。 EGF在糖尿病患者中的作用 IUGR妊娠与EGF对胎儿生化指标的影响有关 和肺的形态成熟。 EGF的研究 影响糖原调节酶和3 H-胆碱掺入。 胎儿注射技术将被用来检查直接影响， EGF对肺部代谢和成熟的影响 体外实验将在 进行了测定葡萄糖浓度梯度对 肺中的成熟事件，包括对EGF结合的影响和对 EGF受体 EGF受体的特性与结合无关 还将研究分析。 EGF的含量 受体自磷酸化在不同的模式和电泳 和蛋白质转移研究，以确定可能的差异， 本身 我们会展开研究，以确定有关款额的可能变动 EGF受体在正常肺中的特异性RNA， 糖尿病和IUGR。 这些研究将确定营养物质改变的机制， 供应（糖尿病和IUGR）与正常成熟事件相互作用。 新 EGF的作用，在肺 这将允许更广泛地了解胎儿成熟的发展 和增长

A central question in perinatal biology is the relationship of substrate supply to overall fetal growth and the development of specialized functions such as surfactant synthesis in lung. We will define relationships between substrate availability and growth factor influences on the biochemical and morphologic maturation of lung and test the hypothesis that substrate supply has important maturational influences, possibly modulated through the interaction of growth factors with receptors on the cell surface. These studies will be focused initially on epidermal growth factor. Two experimental models will be utilized: the fetus of the diabetic rat in which maturation is delayed and those with IUGR exhibiting accelerated maturation. We will characterize EGF binding to cell surface receptors in diabetic and IUGR pregnancies. This will include investigations of the ontogeny of EGF binding in control in experimental fetuses and the effect of insulin reversal of the diabetic state on receptor number and affinity. Immunocytochemical studies will be performed to permit localization of EGF receptors to particular cell types. Changes in EGF binding in diabetic and IUGR pregnancies will be correlated with influences of EGF on biochemical and morphologic maturation of lung. This will include investigation of EGF influences on glycogen regulatory enzymes and 3H-choline incorporation. Fetal injection techniques will be employed to examine direct influences of EGF on lung metabolism and maturation. In vitro experiments will be carried out to determine the effects of graded concentrations of glucose on maturational events in lung including influence on EGF binding and on the EGF receptor. Characteristics of the EGF receptor independent of binding assays will also be investigated. This includes measurements of EGF receptor autophosphorylation in the different models and electrophoretic and protein transfer studies to define possible differences in the receptor itself. We will initiate studies to define possible changes in the amounts of specific RNA's for the EGF receptor in normal lung and in response to diabetes and IUGR. These studies will define mechanisms by which alterations in nutrient supply (diabetes and IUGR) interact with normal maturational events. New information will be provided concerning the role of EGF during lung development which will permit a broader understanding of fetal maturation and growth.