MECHANISMS OF EGF ACTION IN THE FETUS AND NEONATE

假设：表皮生长因子(EGF)促进生长 以及关键的胎儿和婴儿组织的成熟，这些行动 可能导致新的治疗干预模式，以改善 早产儿的生长发育。长期目标： 明确表皮生长因子对组织的作用及其作用机制 胚胎和幼年恒河猴的生长和成熟， 特别强调肠道和肺的发育，并探索 表皮生长因子在早产儿治疗中的应用具体目标：1. 目的：阐明表皮生长因子在胚胎猴体内的作用机制。 区分羊水(口服)和全身反应 胚胎恒河猴(肠外)应用表皮生长因子。2.至 明确肾上腺轴在肾上腺皮质激素作用机制中的作用 胚胎猴的EGF；从初步研究的数据来看，我们 假设循环中肾上腺激素的变化可能起到调节作用 对EGF的一些反应，特别是在肺。3.至 确定胎儿期对EGF的发育和生长反应 在早产中获得任何出生后生长优势 并研究EGF在猕猴体内的重要性。 胎儿和出生后生活的过渡；我们假设EGF 可能有治疗应用来改善婴儿生长发育和 发育，特别是早产儿。方法：表皮生长因子 将通过羊水给胚胎恒河猴(口服和 呼吸途径)或腹膜内(全身)给药 确定哪条路线更有效。一些胎儿会收到 一种肾上腺酶阻滞剂测定胎儿的作用 肾上腺，特别是终止区，在肺和 肠道成熟已经表现出来了。所有的胎儿都将被分娩 在怀孕78%的情况下进行剖腹产；一些将用于 收集组织，而其他婴儿将得到基本的支持- 配对新生儿重症监护病房以确定EGF是否授予 对于早熟的猴子来说，这是一个生存优势。最后，一群 早产儿将只在出生后给予EGF到资产 EGF在出生后的效果。生理生化 将研究肺、肠道和肾上腺的功能，如 他们的组织学会不会。EGF和转化生长因子-αmRNA将在 所有动物决定基因表达的调控 灵长类。

Hypothesis: Epidermal Growth Factor (EGF) stimulates the growth and maturation of crucial fetal and infant tissues, actions that could lead to new modes of therapeutic intervention to improve the growth and development of premature human infants. Long-term Aims: To define the effects and mechanism of action of EGF on tissue growth and maturation in fetal and infant Rhesus monkeys, with particular emphasis on gut and lung development, and to explore the use of EGF for treatment of premature infants. Specific Aims: 1. To elucidate mechanisms of action of EGF in fetal monkeys and to differentiate the responses to amniotic fluid (oral) and systemic (parenteral) administration of EGF in fetal Rhesus monkeys. 2. To define the role of the adrenal axis in the mechanism of action of EGF in fetal monkeys; from the data of the preliminary studies, we postulate that changes in circulating adrenal hormones may mediate some of the responses to EGF, particularly in lung. 3. To determine if the prenatal developmental and growth responses to EGF confer any postnatal growth advantage in prematurely delivered Rhesus monkeys and to examine the importance of EGF in the transition between fetal and postnatal life; we postulate that EGF may have therapeutic applications to improve infant growth and development, particularly in the preterm infant. Methods: EGF will be given to fetal Rhesus monkeys via amniotic fluid (oral and respiratory route) or intraperitoneal (systemic) administration to determine which route is more effective. Some fetuses will receive an adrenal enzyme blocking agent to determine the role of the fetal adrenal gland, in particular the definitive zone, in the lung and gut maturation already demonstrated. All fetuses will be delivered by cesarean section at 78% of gestation; some will be used for tissue collection while other infants will be supported in a pri- mate neonatal intensive care unit to determine whether EGF confers a survival advantage to the premature monkeys. Lastly, a group of premature infants will be given only postnatal EGF to assets the effectiveness of EGF after birth. The physiologic and biochemical function of the lung, gut and adrenal gland will be studied, as will their histology. EGF and TGF-alpha mRNA will be studied in all animals to determine the control of gene expression in the primate.