MATERNAL CORTICOSTEROIDS AND FETAL HOMEOSTASIS

母体皮质类固醇和胎儿体内平衡

• 批准号: 2838838
• 负责人: Maureen Keller-Wood
• 金额: $ 22.21万
• 依托单位: UNIVERSITY OF FLORIDA
• 依托单位国家: 美国
• 财政年份: 1997
• 资助国家: 美国
• 起止时间: 1997-12-22 至 2001-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2838838
• 关键词: adrenalectomy; aldosterone; angiotensin II; arginine vasopressin; atrial natriuretic peptide; blood pressure; blood volume; cortisol; electrolyte balance; embryo /fetus; gestational age; homeostasis; hormone regulation /control mechanism; hypoadrenalism; placental transfer; pregnancy circulation; prenatal stress; sheep; urinalysis

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.

绵羊和人类怀孕期间母体血浆皮质醇 浓度增加至高于非妊娠状态的水平。 该提案的目的是检验以下假设： 怀孕期间的皮质醇浓度对于母体和 胎儿体内平衡。 母体皮质醇浓度是主要的 妊娠大部分时间胎儿皮质醇的来源，因此增加 母体皮质醇可能是胎儿以及母体液体所必需的 胎儿肾上腺皮质成熟前的稳态。 增加 母体皮质醇浓度也可能间接影响胎儿 通过控制母体体液平衡和子宫血流实现体内平衡。 拟议的研究将比较液体平衡和相关的激素 在六种不同的实验中影响母羊和胎儿的体内平衡 组别：正常怀孕母羊和肾上腺切除的怀孕母羊 将皮质醇替换至极低的血浆浓度或正常 怀孕母羊的浓度，或用皮质醇替代 正常水平，但醛固酮低于正常水平；我们将 还包括皮质醇或醛固酮被替代的两组 尽管母体皮质醇下降或 醛固酮水平。 我们假设母亲皮质醇减少 将导致加压素和肾素-血管紧张素的激活 母体内的系统和经胎盘液体流量减少和/或 子宫血流量减少，这会导致慢性缺氧 以及胎儿生长迟缓。 我们预测这种模式将 与血浆醛固酮减少观察到的结果不同。 我们预测这种模式将与观察到的模式不同 血浆醛固酮减少。 我们预测减少 母体皮质醇和/或水输送给胎儿会导致 作为补偿，降低胎儿尿液和肺液体产生率 维持胎儿压力和血容量的机制。 基础值 胎儿和母体的血容量和血压、血浆电解质和 血浆蛋白浓度以及胎儿和母体加压素， 肾素活性和心房钠肽将在 110-125 测量 妊娠天数，胎儿肾上腺分泌大量肾上腺素之前 皮质醇的量。 胎儿和母体的血流分布和 胎儿尿流量和肺液体产生量也将被测量 检验胎儿会尝试调节血液的假设 通过流体守恒获得压力和体积。 这些结果 研究将表明胎儿的体积稳态是否取决于 对母体皮质醇浓度的影响。