CONTROL OF LIPOPROTEIN AND STEROID LEVELS IN THE FETUS

冠心病的风险增加的人谁长期 胆固醇的血液浓度升高被广泛接受。 以识别 许多研究人员测量了高胆固醇血症的婴儿的脐带血， 血胆固醇，胆固醇酯，偶尔分布 胆固醇在各种脂蛋白中。 这种确定的效用是 这取决于这样的假设，即脐带中的胆固醇浓度 血液是由基因决定的 我们和其他人发现， 脐带血中胆固醇浓度低， 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 胎儿在子宫内受到压力的几种情况，由于 产妇高血压、糖尿病、缺氧等原因，产妇 雌三醇的血浆浓度下降。 由于LDL-胆固醇似乎 胎儿肾上腺类固醇生成的优选底物导致显著的 脐带血LDL-胆固醇水平升高。 为了验证这个假设， 我们建议测定胆固醇、胆固醇酯和 脐带血中胆固醇在脂蛋白中的分布， 正常孕妇和妊娠并发症孕妇的母体血液 如慢性高血压、妊娠高血压、糖尿病 和胎儿发育迟缓 获取胎儿肾上腺 在这些怀孕的生物合成活性，我们将测量雌三醇在孕产妇 血浆和脐带血在分娩时。 我们还将利用胎儿 组织，例如，肝、肠、肺和胎盘的器官培养， 研究人类胎儿中脂蛋白的起源。 的结果 拟议的调查应有助于深入了解控制 雌三醇水平在母体隔室，应该提供深入了解 引起胎儿肾上腺变化的生理适应 类固醇生成，并确定LDL在 人胎儿肾上腺皮质的类固醇合成。

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.