NEUROENDOCRINE MATURATION

神经内分泌成熟

• 批准号: 6241180
• 负责人: James F Padbury
• 金额: $ 7.84万
• 依托单位: LUNDQUIST INSTITUTE FOR BIOMEDICAL INNOVATION AT HARBOR-UCLA MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 1997
• 资助国家: 美国
• 起止时间: 1997-04-01 至 1998-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6241180
• 关键词: adrenergic receptor; adrenocorticotropic hormone; catecholamines; colorimetry; combination chemotherapy; corticosteroids; environmental adaptation; epidermal growth factor; gestational age; growth /development; hormone receptor; hormone therapy; neuroendocrine system; physiology; premature infant animal; prolactin; radioimmunoassay; second messengers; sheep; thyroid hormones

Successful transition from fetal to neonatal life depends upon the integration of key neuroendocrine systems: sympathoadrenal, thyroid and adrenocortical. The developmentally programmed changes which occur in these systems represent key maturational signals for the developing mammalian fetus. Pharmacologic manipulation of these systems has evolved as a strategy to induce maturation in the preterm fetus. Antenatal corticosteroid treatment is a clinical routine to accelerate fetal lung maturation in infants at risk for preterm delivery. In contrast, there is less information on the effect of antenatal corticosteroids on postnatal function of other major organ systems. Our central hypothesis is that pharmacologic fetal maturation strategies which are clinically successful have significant maturational effects on these three neuroendocrine systems. Acceleration of neuroendocrine maturation in turn will result in improvements in postnatal adaptation, thus facilitating a reduction in non-pulmonary neonatal morbidity and mortality. To test this hypothesis, we will compare physiologic adaptation to extrauterine life in preterm, newborn fetal sheep which have been treated with a variety of maturational agents (corticosteroids, thyroid hormones, EGF) alone and in combination. Mechanisms for the action of these agents at the level of circulating hormones (catecholamines, thyroid hormones, cortisol, prolactin), receptors (adrenergic receptors, nuclear thyroid receptors) and second messenger systems (adenylyl cyclase) will be investigated. The doses, treatment strategies and routes of administration have been chosen to provide the most clinically relevant results. Parallel studies are proposed in fetal/newborn sheep and in human preterm infants enrolled in an ongoing clinical trial of the effect of betamethasone alone and in combination with thyrotropin releasing hormone.

从胎儿到新生儿生活的成功过渡取决于 关键神经内分泌系统的整合：交感神经，甲状腺和 肾上腺皮质。 在 这些系统代表了开发的关键成熟信号 哺乳动物胎儿。 这些系统的药理操作已经发展 作为诱导早产胎儿成熟的策略。 产前 皮质类固醇治疗是加速胎儿肺的临床常规 婴儿早产风险的婴儿成熟。 相反，那里 是较少有关产前皮质类固醇对的影响的信息 其他主要器官系统的产后功能。 我们的中心假设 是临床上的药理学胎儿成熟策略 成功对这三个 神经内分泌系统。 神经内分泌成熟的加速 转弯将导致产后适应的改善，因此 促进降低非肺部新生儿发病率和 死亡。 为了检验这一假设，我们将比较生理 适应早产，新生胎儿绵羊的外界生活 已经用多种成熟剂（皮质类固醇， 甲状腺激素，单独和组合。 机制 这些药物在循环激素水平上的作用 （儿茶酚胺，甲状腺激素，皮质醇，催乳素），受体 （肾上腺素能受体，核甲状腺受体）和第二信使 将研究系统（腺苷酸环化酶）。 剂量，治疗 选择了策略和行政途径以提供 大多数临床相关的结果。 提出了平行研究 胎儿/新生绵羊和人类早产婴儿正在进行 单独和组合倍吐饭的影响的临床试验 甲状腺激素释放激素。