CONTROL OF LIPOPROTEIN AND STEROID LEVELS IN THE FETUS

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We previously have provided evidence that (1) steroidogenesis in the human fetal adrenal, which is normally accelerated during the last 6-10 weeks of gestation, is impaired in newborns of women with pregnancy complication (hypertension, diabetes, severe infections); (2) plasma lipoproteins, particularly low-density lipoproteins (LDL). facilitate fetal adrenal steroid secretion in vitro; (3) fetal plasma levels of cholesterol (c), especially LDL-C, appear to be regulated, in part, by the rate of uptake by the fetal adrenals, being high when the adrenal is quiescent and being low when adrenal activity is highest; (4) lung maturation appears to be related to the endocrine milieu of the fetus, especially those hormones produced directly or indirectly from the fetal adrenal. Thus, we purpose (1) to define the trophic regulation of the fetal adrenal during normal and complicated pregnancy by quantifying fetal plasma ACTH and other POMC-derived peptides throughout the latter half of gestation under varied circumstances of maternal/fetal health; (2) to elucidate mechanisms for the seemingly independent function of the fetal and neocortical zones of the human fetal adrenal by evaluating the utilization in steroidogenesis of lipoprotein-C assimilated by receptor- mediated and receptor-independent pathways and of C synthesized de novo in the separated zones of the fetal adrenal, processes as well as the production of steroidogenic enzymes and the LDL receptor in the fetal adrenal; and (4) to define the factors that regulate fetal plasma lipoproteins by investigating apolipoprotein synthesis by the fetal liver and by quantifying fatal plasma lipoprotein-c and apolipoproteins during normal and complicated pregnancy. The results of these studies should be fundamental to an understanding of several aspects of fetal development and of the differential regulation of zonal function in the adrenal and lipoprotein homeostasis during postnatal life.