MATERNAL CORTICOSTEROIDS AND FETAL HOMEOSTASIS

母体皮质类固醇和胎儿体内平衡

• 批准号: 6125578
• 负责人: Maureen Keller-Wood
• 金额: $ 22.88万
• 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/6125578
• 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.

在绵羊和人类中怀孕期间孕妇血浆皮质醇 浓度在非怀孕状态下的水平高于水平。 该提议的目的是检验以下假设。 皮质醇的妊娠浓度对于母亲和 胎儿体内平衡。 母体皮质醇浓度是主要的 因此，妊娠的大部分胎儿皮质醇来源增加 母体皮质醇可能是胎儿以及母体流体所必需的 胎儿肾上腺皮质成熟之前的稳态。 增加 母体皮质醇浓度也可能间接促进胎儿 通过控制母体液体平衡和子宫血流来稳态。 拟议的研究将比较流体平衡和与激素相关的研究 在六个不同的实验中，在母羊和胎儿中体内稳态 组：正常的怀孕母羊和孕妇的肾上腺病母羊 将皮质醇替换为非常低的血浆浓度或正常 怀孕母羊的浓度，或取代皮质醇 正常水平，但醛固酮低于正常水平；我们将 还包括两组，其中替换了皮质醇或醛固酮 尽管孕妇皮质醇降低或 醛固酮水平。 我们假设减少母体皮质醇 会导致加压素和肾素 - 血管紧张素的激活 母亲的系统，减少了移植液通量和/或 子宫血流降低，这导致慢性缺氧 和胎儿的生长迟缓。 我们预测这种模式将 与血浆醛固酮减少观察到的不同。 我们预测，这种模式将与观察到的模式不同 减少血浆醛固酮。 我们预测减少 母体皮质醇和/或向胎儿输送水将导致 胎儿尿液和肺液体产量降低作为补偿性 维持胎儿压力和血液体积的机制。 基础值 胎儿和母体血容量和压力，血浆电解质和 血浆蛋白浓度以及胎儿和母体加压素， 肾素活性和心房自然肽将在110-125测量 妊娠日，在胎儿肾上腺分泌之前明显 皮质醇的数量。 胎儿和母体血流分布， 胎儿尿液流量和肺液体产生也将被测量 检验胎儿将试图调节其血液的假设 压力和体积通过液体保护。 这些结果 研究将表明胎儿中的体内稳态是否取决于 在母体皮质醇浓度上。