MECHANISMS OF EGF ACTION IN THE FETUS AND NEONATE

表皮生长因子（EGF）刺激生长 以及重要的胎儿和婴儿组织的成熟， 可能导致新的治疗干预模式，以改善 人类早产儿的生长和发育。 长期目标： EGF的作用和机制 恒河猴胎儿和婴儿的生长和成熟， 特别强调肠道和肺部的发育，并探索 EGF治疗早产儿 具体目标：1。 阐明EGF在胎猴中的作用机制， 区分对羊水（口服）和全身的反应 在胎恒河猴中的EGF（肠胃外）施用。 2.到 确定肾上腺轴在以下作用机制中的作用： EGF在胚胎猴;从初步研究的数据，我们 假设循环肾上腺激素的变化可能介导 EGF的作用，特别是在皮肤上。 3.到 确定是否产前发育和生长反应的EGF 在早产儿中赋予任何出生后生长优势 研究EGF在皮肤中的重要性。 胎儿和产后生活之间的过渡;我们假设EGF 可用于改善婴儿生长的治疗应用， 特别是在早产儿中。 方法：EGF 将通过羊水（口服和 呼吸途径）或腹膜内（全身）给药， 确定哪条路线更有效。 有些胎儿会接受 肾上腺酶阻断剂，以确定胎儿的作用 肾上腺，特别是肺中的限定区， 肠道成熟已经证明。 所有的胎儿都将在 在78%的妊娠期进行剖宫产;有些将用于 组织收集，而其他婴儿将在一个初步支持， 配合新生儿重症监护病房，以确定是否EGF赋予 早产猴的生存优势 最后，一组 早产儿将只给予出生后的EGF资产， EGF的功效 生理生化 将研究肺、肠道和肾上腺的功能， 他们的组织学。 EGF和TGF-α mRNA将在 所有动物，以确定基因表达的控制， 灵长类动物

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.