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.

宫内环境的异常可能是急性或慢性 自然，与围产期发病率的增加有关 死亡。 例如，生长迟钝的胎儿无法 子宫血流（UBF）的耐受性降低，异常证明 Apgar得分，胎粪染色的羊水的发生， 围产期死亡率增加。 了解胎儿对这些的反应 不良宫内事件是基于理解复合物的 可能发生的综合生理反应。 因此，宽阔 该项目的目的是描绘和整合神经肿瘤， 与胎儿“困扰”有关的心血管和代谢事件。 这 具体目的是确定：精氨酸加压素（AVP）是否为 对于释放其他神经肿瘤剂的释放很重要 胎儿“困扰”，例如Acth和Cortisol，并描绘他们 相互作用;如果在胎儿AVP释放之间存在相互作用，请使用胰高血糖素 分泌和葡萄糖稳态；如果之间存在相互作用 胎儿“遇险”期间的儿茶酚胺（C）和AVP；最后，什么是 胎儿“压力”期间催乳素（PRL）分泌的模式及 与AVP和ACTH的相互作用。 为了实现这些目标，研究已经 设计利用长期蒙受的怀孕母羊和胎儿绵羊的设计 研究了远离手术的遥远，在怀孕的最后三分之一，110天 术语（术语= 144+5天）。 激素分泌和相互作用的模式 将从在，期间，之中和 实验干预后，通过放射免疫测定测量激素 （AVP，C，ACTH，PRL和皮质醇），同时不断监测UBF，心脏 速率，血压，羊水压力，O2含量和动脉 母亲和胎儿中的PO2，PCO2和pH。 在选定的研究血液中 将确定葡萄糖和乳酸，并改变胎儿区域 使用放射性标记的微球评估的血流。 AVP在 将通过监测检查胎儿胎粪释放的发病机理 胃肠道内压力，即蠕动。 学位 胎儿“遇险”将通过急性减少UBF而获得。 C和/或动脉血管阻塞。 最后，AVP的行动 （Neurohumoral，心血管或代谢）将使用被动阻止 用AVP抗抗菌免疫。 从这些研究的结果 更好地了解胎儿适应宫内“压力”和 将获得激素相互作用。