FETAL HORMONAL ADAPTATION TO INTRAUTERINE STRESS

胎儿激素对宫内压力的适应

• 批准号: 3319107
• 负责人: CHARLES RICHARD ROSENFELD
• 金额: $ 16.04万
• 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/3319107
• 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.

子宫内环境的异常可能是急性的或慢性的， 与围产期发病率增加有关， mortality. 例如，生长迟缓的胎儿 耐受子宫血流量（UBF）降低，如异常 Apgar评分、羊水粪染的发生率，以及 围产期死亡率增加。 了解胎儿对这些的反应 子宫内不良事件是基于对复杂的 可能发生的综合生理反应。 因此， 该项目的目的是描绘和整合神经体液， 与胎儿“窘迫”相关的心血管和代谢事件。“这位 具体目的是确定：精氨酸加压素（AVP）是否 重要的是在释放其他神经体液剂升高的反应 胎儿“窘迫”，例如，促肾上腺皮质激素和皮质醇，并描绘他们的 相互作用;如果胎儿AVP释放、胰高血糖素 分泌和葡萄糖稳态;如果存在相互作用， 胎儿“窘迫”期间的儿茶酚胺（C）和AVP;最后， 胎儿“应激”时催乳素（PRL）分泌模式及其与妊娠结局的关系 与AVP和ACTH相互作用。 为了实现这些目标，已经进行了研究。 设计利用长期仪器怀孕母羊和胎羊 研究远离手术，在怀孕的最后三分之一，110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、期间和之后获得的系列观察结果确定 在实验性干预后，通过放射免疫测定法测量激素 (AVP，C，ACTH，PRL和皮质醇），同时连续监测UBF，心脏 心率、血压、羊水压、O2含量和动脉 母亲和胎儿的PO 2、PCO 2和pH值。 在选定的研究中， 葡萄糖和乳酸将被确定，胎儿区域的变化， 使用放射性标记的微球评价血流。 AVP的作用 胎儿胎粪释放的发病机制将通过监测来检查， 胃肠腔内压力，即，- 是的 程度的 胎儿“窘迫”将通过输注急剧降低UBF获得 和/或动脉血管封堵器。 最后，AVP的作用 （神经体液，心血管或代谢）将被阻断使用被动 用AVP-抗血清免疫。 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， 将获得激素相互作用。