FETAL HORMONAL ADAPTATION TO INTRAUTERINE STRESS

胎儿激素对宫内压力的适应

• 批准号: 3319105
• 负责人: CHARLES RICHARD ROSENFELD
• 金额: $ 16.76万
• 依托单位: UT SOUTHWESTERN MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 1986
• 资助国家: 美国
• 起止时间: 1986-09-01 至 1989-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3319105
• 关键词: adrenocorticotropic hormone; arginine vasopressin; blood glucose; cardiovascular function; catecholamines; centrifugation; cortisol; embryo /fetus death; embryo /fetus hypoxia; environmental adaptation; gastrointestinal motility /pressure; glucagon; hormone regulation /control mechanism; metabolism; pancreatic islet function; pregnancy circulation; pregnancy disorder; pregnancy loss; prenatal growth disorder; prenatal stress; prolactin; radioimmunoassay; radionuclide diagnosis; radiotracer; respiratory gas analyzer; scintillation spectrometry

Abnormalities of the intrauterine environment may be acute or chronic in nature and are associated with increased perinatal morbidity and mortality. For example, fetuses with growth retardation are less able to tolerate decreases in uterine blood flow (UBF) as evidenced by abnormal Apgar Scores, the occurrence of meconium-stained amniotic fluid, and increased perinatal mortality. Understanding the fetal responses to these adverse intrauterine events is predicated upon understanding the complex integrated physiologic responses that might occur. Thus, the broad objective of this project is to delineate and integrate neurohumoral, cardiovascular, and metabolic events associated with fetal "distress." The specific aims are to determine: whether arginine vasopressin (AVP) is important in the release of other neurohumoral agents elevated in response to fetal "distress", e.g., ACTH and cortisol, and delineate their interaction; if an interaction exists between fetal AVP release, glucagon secretion, and glucose homeostasis; if interactions exist between catecholamines (C) and AVP during fetal "distress"; and finally, what is the pattern of prolactin (PRL) secretion during fetal "stress" and its interaction with AVP and ACTH. To accomplish these aims, studies have been designed utilizing chronically-instrumented pregnant ewes and fetal sheep studied remote from surgery and in the last third of pregnancy, 110 days to term (term=144+5 days). The patterns of hormonal secretion and interaction will be determined from serial observations obtained before, during, and after an experimental intervention, measuring hormones by radioimmunoassay (AVP, C, ACTH, PRL, and cortisol), while continuously monitoring UBF, heart rate, blood pressure, amniotic fluid pressure, O2 content, and arterial PO2, PCO2, and pH in the mother and fetus. In selected studies blood glucose and lactate will be determined and alterations in fetal regional blood flows evaluated using radiolabelled microspheres. The role of AVP in the pathogenesis of fetal meconium release will be examined by monitoring gastrointestinal intraluminal pressure, i.e., peristalsis. Degrees of fetal "distress" will be obtained by acutely decreasing UBF with infusions of C and/or arterial vascular occluders. Finally, the actions of AVP (neurohumoral, cardiovascular, or metabolic) will be blocked using passive immunization with AVP-antiserum. From the results of these studies a better understanding of fetal adaptation to intrauterine "stress" and hormonal interaction will be obtained.

宫内环境异常可能是急性的，也可能是慢性的。 性质并与围产期发病率增加有关 死亡。 例如，生长迟缓的胎儿的能力较差。 耐受子宫血流量（UBF）减少，如异常所证明 阿普加评分、羊水胎粪染色的发生率，以及 围产期死亡率增加。 了解胎儿对这些的反应 宫内不良事件的发生取决于对复杂情况的了解 可能发生的综合生理反应。 因此，广泛的 该项目的目标是描述和整合神经体液， 与胎儿“窘迫”相关的心血管和代谢事件。 这 具体目标是确定： 精氨酸加压素 (AVP) 是否 对于响应升高的其他神经体液药物的释放很重要 胎儿的“痛苦”，例如促肾上腺皮质激素和皮质醇，并描绘出它们的 相互作用;如果胎儿 AVP 释放与胰高血糖素之间存在相互作用 分泌和葡萄糖稳态；如果之间存在相互作用 胎儿“窘迫”期间的儿茶酚胺 (C) 和 AVP；最后，什么是 胎儿“应激”期间催乳素（PRL）的分泌模式及其 与 AVP 和 ACTH 相互作用。 为了实现这些目标，研究人员进行了 利用长期接受检测的怀孕母羊和胎羊设计 研究远离手术，在怀孕的最后三分之一，即 110 天 期限（期限=144+5天）。 荷尔蒙分泌和相互作用的模式 将根据之前、期间和期间获得的连续观察来确定 实验干预后，通过放射免疫测定法测量激素 （AVP、C、ACTH、PRL 和皮质醇），同时持续监测 UBF、心脏 心率、血压、羊水压、O2 含量和动脉 母亲和胎儿的 PO2、PCO2 和 pH 值。 在选定的研究中，血液 将测定葡萄糖和乳酸以及胎儿区域的变化 使用放射性标记的微球评估血流。 AVP的作用 通过监测来检查胎儿胎便释放的发病机制 胃肠道腔内压力，即蠕动。 度数 胎儿“窘迫”将通过输注急剧减少UBF来实现 C 和/或动脉血管封堵器。 最后，AVP的动作 （神经体液、心血管或代谢）将被被动阻断 用 AVP 抗血清进行免疫。 从这些研究的结果来看 更好地了解胎儿对宫内“压力”的适应 将获得荷尔蒙相互作用。