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: 3322936
• 负责人: Charles RICHARD PARKER
• 金额: $ 11.56万
• 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 1994-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3322936
• 关键词: adrenal glands; adrenocorticotropic hormone; apolipoproteins; blood lipoprotein biosynthesis; blood lipoprotein metabolism; cholesterol; embryo /fetus; enzyme mechanism; gel electrophoresis; gestational diabetes mellitus; high performance liquid chromatography; hormone regulation /control mechanism; human fetus tissue; human pregnant subject; human subject; immunodiffusion; longitudinal human study; low density lipoprotein; mammalian embryology; 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

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.

我们以前提供的证据表明：(1)类固醇的合成 人胎儿肾上腺，通常在最后6-10个月加速 怀孕数周，对怀孕妇女的新生儿有损害 并发症(高血压、糖尿病、严重感染)；(2)血浆 脂蛋白，尤其是低密度脂蛋白。利便 胎儿肾上腺类固醇激素的体外分泌；(3)胎儿血浆中 胆固醇(C)，特别是低密度脂蛋白-C，似乎部分受 胎儿肾上腺的摄取率，当肾上腺处于 静息，肾上腺活动最高时低；(4)肺 成熟似乎与胎儿的内分泌环境有关， 尤其是那些直接或间接从胎儿体内产生的激素 肾上腺。因此，我们的目的是(1)定义 胎儿肾上腺在正常妊娠和复杂妊娠中的定量研究 胎儿血浆促肾上腺皮质激素和其他POMC衍生的多肽 在母婴健康状况不同的情况下半孕期； (2)阐明看似独立的功能的机制 通过评估人胎儿肾上腺的胎儿和新皮质区 受体同化的脂蛋白-C在类固醇合成中的应用 介导和受体非依赖性途径与C合成从头合成 在胎儿肾上腺的不同区域，突起以及 胎儿类固醇生成酶和低密度脂蛋白受体的产生 肾上腺；以及(4)确定调节胎儿血浆的因素 胎肝载脂蛋白合成的研究 并通过量化致命的血浆脂蛋白-c和载脂蛋白 正常妊娠和复杂妊娠。这些研究的结果应该是 了解胎儿发育的几个方面的基础 以及肾上腺和肾上腺的区带功能的不同调节 出生后生活中的脂蛋白稳态。