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: 3322942
• 负责人: Charles RICHARD PARKER
• 金额: $ 13.44万
• 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/3322942
• 关键词: adrenal glands; adrenocorticotropic hormone; apolipoproteins; blood lipoprotein biosynthesis; blood lipoprotein metabolism; cholesterol; embryo /fetus; enzyme mechanism; female; 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); nonblood lipoprotein; 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.

我们之前提供的证据表明（1）类固醇生成 人类胎儿肾上腺，通常在最后 6-10 天内加速 怀孕几周后，怀孕妇女的新生儿会受到损害 并发症（高血压、糖尿病、严重感染）； (2) 血浆 脂蛋白，特别是低密度脂蛋白（LDL）。促进 体外胎儿肾上腺类固醇分泌； (3)胎儿血浆水平 胆固醇 (c)，尤其是 LDL-C，似乎部分受到调节 胎儿肾上腺的吸收率，当肾上腺处于高水平时，吸收率较高 当肾上腺活动最高时处于静止状态并处于低水平； (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由胎儿产生的激素 肾上腺。因此，我们的目的（1）定义了 通过量化正常和复杂妊娠期间的胎儿肾上腺 胎儿血浆 ACTH 和其他 POMC 衍生肽贯穿后者 在不同的孕产妇/胎儿健康状况下妊娠的一半； (2) 阐明看似独立的功能的机制 通过评估人类胎儿肾上腺的胎儿和新皮质区域 受体同化的脂蛋白-C 在类固醇生成中的利用 介导且不依赖于受体的途径以及 C 从头合成 在胎儿肾上腺的分离区域，过程以及 胎儿体内类固醇生成酶和低密度脂蛋白受体的产生 肾上腺; (4) 定义调节胎儿血浆的因素 通过研究胎儿肝脏的载脂蛋白合成来分析脂蛋白 并通过定量致命血浆脂蛋白-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 对于了解胎儿发育的几个方面至关重要 以及肾上腺和区域功能的差异调节 产后生活中的脂蛋白稳态。