CONTROL OF LIPOPROTEIN AND STEROID LEVELS IN THE FETUS

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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.