CONTROL OF LIPOPROTEIN AND STEROID LEVELS IN THE FETUS

胎儿脂蛋白和类固醇水平的控制

• 批准号: 3322940
• 负责人: Charles RICHARD PARKER
• 金额: $ 11.62万
• 依托单位: UNIVERSITY OF ALABAMA AT BIRMINGHAM
• 依托单位国家: 美国
• 财政年份: 1986
• 资助国家: 美国
• 起止时间: 1986-07-01 至 1989-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3322940
• 关键词: adrenal glands; adrenocorticotropic hormone; blood lipoprotein biosynthesis; blood lipoprotein metabolism; cholesterol; dehydroepiandrosterone; embryo /fetus; estriol; gel electrophoresis; hormone regulation /control mechanism; human subject; hypertension; immunodiffusion; lipoprotein lipase; longitudinal human study; low density lipoprotein; newborn human (0-6 weeks); organ culture; pregnancy circulation; pregnancy disorder; pregnancy toxemia /hypertension; prenatal stress; radioimmunoassay; scintillation spectrometry; statistics /biometry; steroid biosynthesis; steroid sulfate; umbilical cord; very low density lipoprotein

The increased risk of coronary heart disease in persons who have chronically elevated blood concentrations of cholesterol is widely accepted. To identify infants at risk of hypercholesterolemia, many investigators have measured cord blood cholesterol, cholesterol esters, and occasionally the distribution of cholesterol among various lipoproteins. The utility of such determinations is dependent upon the assumption that the concentrations of cholesterol in cord blood is genetically predetermined. We, and others, have found that the possibility exists that the cord blood concentrations of cholesterol in low density lipoprotein (LDL) is perhaps more related to the rate of LDL cholesterol utilization in the biosynthesis of steroids by the fetal adrenal cortex. In several instances in which the fetus is subjected to stress in utero, due to maternal hypertension, diabetes mellitus, anoxia, and other causes, maternal plasma concentrations of estriol decline. Since LDL-cholesterol appears to be the preferred substrate for fetal adrenal steroidogenesis results in marked elevations in the cord blood level of LDL-cholesterol. To test this hypothesis, we propose to determine the level of cholesterol, cholesterol esters, and the distribution of cholesterol among the lipoproteins in umbilical cord blood and maternal blood in both normal as well as in pregnancies complicated by factors such as chronic hypertension, pregnancy-induced hypertension, diabetes mellitus, and fetal growth retardation. To obtain evidence of the extent of fetal adrenal biosynthetic activity in these pregnancies, we will measure estriol in maternal plasma and in cord blood at the time of delivery. We will also utilize fetal tissues, e.g., liver, intestine, lung, and placenta in organ culture to investigate the origin of lipoproteins in the human fetus. The results of the proposed investigations should ppovide insight into the mechanisms which control estriol levels in the maternal compartment, should provide insight into the physiologic adaptations that give rise to changes in fetal adrenal steroidogenesis, and define the kinetics of the utilization of LDL in steroidogenesis by the human fetal adrenal cortex.

长期患有冠心病的人患冠心病的风险增加 血液中胆固醇浓度升高已被广泛接受。 识别 婴儿有高胆固醇血症的风险，许多研究人员测量了脐带血 血液中的胆固醇、胆固醇酯，以及偶尔的分布 各种脂蛋白中的胆固醇。 这种决定的效用是 取决于脐带中胆固醇浓度的假设 血液是基因决定的。 我们和其他人发现 存在这样的可能性：脐带血中胆固醇浓度较低 密度脂蛋白（LDL）可能与 LDL 胆固醇的比率更相关 胎儿肾上腺皮质在类固醇生物合成中的利用。 在 在一些情况下，胎儿在子宫内承受压力，原因是 产妇高血压、糖尿病、缺氧等原因，产妇 血浆雌三醇浓度下降。 由于低密度脂蛋白胆固醇似乎 胎儿肾上腺类固醇生成的首选底物导致显着 脐带血低密度脂蛋白胆固醇水平升高。 为了检验这个假设， 我们建议测定胆固醇、胆固醇酯和胆固醇的水平 脐带血中胆固醇在脂蛋白中的分布 正常以及因因素而复杂的妊娠中的母血 如慢性高血压、妊娠高血压、糖尿病、 和胎儿生长迟缓。 获得胎儿肾上腺程度的证据 这些怀孕期间的生物合成活性，我们将测量母体中的雌三醇 分娩时的血浆和脐带血中。 我们还将利用胎儿 器官培养中的组织，例如肝、肠、肺和胎盘 研究人类胎儿脂蛋白的起源。 结果 拟议的调查应提供对控制机制的深入了解 母体室中的雌三醇水平，应该可以深入了解 引起胎儿肾上腺变化的生理适应 类固醇生成，并定义 LDL 的利用动力学 人类胎儿肾上腺皮质的类固醇生成。