SUBSTRATE AND ENDOCRINE INFLUENCES ON DEVELOPING LUNG

围产期生物学的一个中心问题是底物之间的关系。 为胎儿的全面发育和特殊功能的发展提供营养 如肺内表面活性物质的合成。我们将定义以下之间的关系 底物利用率和生长因子对生物化学和生物化学的影响 肺的形态成熟和检验底物的假说 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。二 将利用的实验模型：糖尿病大鼠的胚胎 哪种成熟延迟，而IUGR表现为加速成熟 成熟。我们将表征EGF与细胞表面受体的结合 糖尿病和IUGR妊娠。这将包括对 实验性胎儿EGF结合的个体发育及对其的影响 胰岛素逆转糖尿病状态对受体数量和亲和力的影响。 将进行免疫细胞化学研究，以允许EGF的定位 特定细胞类型的受体。糖尿病和糖尿病患者表皮生长因子结合力的变化 胎儿宫内发育迟缓与表皮生长因子对生化指标的影响 肺组织形态成熟。这将包括对EGF的调查 对糖原调节酶和~3H-胆碱掺入的影响。 将使用胎儿注射技术来检查 表皮生长因子对肺代谢和成熟的影响。体外实验将是 以确定不同浓度的葡萄糖对 肺成熟事件包括对EGF结合的影响和对EGF的影响 EGF受体。不依赖结合的EGF受体的特性 化验也将被调查。这包括对EGF的测量 不同模型和电泳法中的受体自磷酸化 和蛋白质转移研究，以确定受体可能的差异 它本身。我们将展开研究，以确定可能发生的金额变化。 在正常肺组织中EGF受体的特异性RNA的表达 糖尿病和宫内发育迟缓。 这些研究将确定营养物质变化的机制 供应(糖尿病和IUGR)与正常成熟事件相互作用。新的 将提供有关EGF在肺中的作用的信息 这将允许对胎儿成熟有更广泛的了解 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.