MATERNAL CORTICOSTEROIDS AND FETAL HOMEOSTASIS

绵羊和人类在怀孕期间的母体血浆皮质醇 在非怀孕状态下，浓度会增加到水平以上。 这项提议的目标是检验这样一种假设，即 孕期皮质醇浓度对母体和 胎儿动态平衡。母体皮质醇浓度是主要的 因此，孕期大部分时间胎儿皮质醇的来源增加 母体皮质醇可能是胎儿和母体体液所必需的 胎儿肾上腺皮质成熟前的动态平衡。增加了 母体皮质醇浓度也可能间接导致胎儿 通过控制母体体液平衡和子宫血流来实现动态平衡。 拟议的研究将比较液体平衡和相关的激素。 在六种不同实验中对母羊和胎儿体内容量稳态的影响 组：正常妊娠母羊和去肾上腺妊娠母羊 将皮质醇替换至极低的血浆浓度或恢复正常 怀孕母羊的浓度，或用皮质醇替代 但醛固酮水平正常但低于正常水平；我们会 还包括两组取代皮质醇或醛固酮的组 恢复到正常水平，尽管母体皮质醇或 醛固酮水平。我们假设母体皮质醇减少 会导致血管加压素和肾素-血管紧张素的激活 母亲体内的系统和经胎盘液体流量减少和/或 子宫血流量减少，导致慢性缺氧 和胎儿发育迟缓。我们预测，这种模式将 与血浆醛固酮降低时观察到的情况不同。 我们预测，这一模式将不同于 降低血浆醛固酮水平。我们预测，减少 母体皮质醇和/或水给胎儿会导致 代偿性减少胎儿尿液和肺液产生率 维持胎儿血压和血量的机制。的基本值 胎儿和母亲的血容量和血压，血浆电解质和 血浆蛋白浓度以及胎儿和母亲的加压素， 肾素活性和心房天然多肽将在110-125测量 妊娠天数，在胎儿肾上腺分泌明显之前 皮质醇的含量。胎儿和母体血流分布及 胎儿尿流量和肺液产量也将被测量到 检验胎儿将试图调节其血液的假设 压力和体积通过流体守恒。这些研究的结果 研究将表明，胎儿体内的体积动态平衡是否取决于 母体皮质醇浓度。

During pregnancy in sheep and in human beings maternal plasma cortisol concentrations are increased above the level in the nonpregnant state. The goal of this proposal is to test the hypothesis that the elevated cortisol concentrations of pregnancy are essential for maternal and fetal homeostasis. Maternal cortisol concentrations are the primary source of fetal cortisol for much of gestation, therefore, increased maternal cortisol may be necessary for fetal, as well as maternal, fluid homeostasis before maturation of the fetal adrenal cortex. Increased maternal cortisol concentrations may also indirectly contribute to fetal homeostasis by control of maternal fluid balance and uterine blood flow. The proposed studies will compare fluid balance and the hormones related to volume homeostasis in the ewe and fetus in six different experimental groups: normal pregnant ewes, and pregnant adrenalectomized ewes given replacement of cortisol to very low plasma concentrations or to normal concentrations for a pregnant ewe, or with replacement of cortisol to normal levels but aldosterone to lower than than normal levels; we will also include two groups in which cortisol or aldosterone are replaced to normal levels in the fetus, despite decreased maternal cortisol or aldosterone levels. We hypothesize that decreased maternal cortisol will result in activation of vasopressin and the renin-angiotensin system in the mother and decreased transplacental fluid flux and/or decreased uterine blood flow, and that this results in chronic hypoxia and growth retardation of the fetus. We predict that this pattern will be different than that observed with reduction of plasma aldosterone. We predict that this pattern will be different than that observed with reduction of plasma aldosterone. We predict that the reduction of maternal cortisol and/or water delivery to the fetus will result in reduced fetal urine and lung liquid production rates as compensatory mechanism to maintain fetal pressure and blood volume. Basal values for fetal and maternal blood volume and pressure, plasma electrolyte and plasma protein concentrations and for fetal and maternal vasopressin, renin activity and atrial naturietic peptide will be measured at 110-125 days of gestation, before the fetal adrenal secretes appreciable quantities of cortisol. Fetal and maternal blood flow distribution and fetal urine flow and lung liquid production will also be measured to test the hypothesis that the fetus will attempt to regulate its blood pressure and volume through fluid conservation. The results of these studies will indicate whether volume homeostasis in the fetus depends on maternal cortisol concentration.