STEROL SYNTHESIS AND LOW-DENSITY LIPOPROTEIN CLEARANCE INVIVO IN THE PREGNANT RAT, PLACENTA, AND FETUS - SOURCES FOR TISSUE CHOLESTEROL DURING FETAL DEVELOPMENT

STEROL SYNTHESIS AND LOW-DENSITY LIPOPROTEIN CLEARANCE INVIVO IN THE PREGNANT RAT, PLACENTA, AND FETUS - SOURCES FOR TISSUE CHOLESTEROL DURING FETAL DEVELOPMENT
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DOI:
10.1172/jci113829
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发表时间:
1988-12-01
影响因子:
15.9
通讯作者:
DIETSCHY, JM
DIETSCHY, JM
中科院分区:
医学1区
文献类型:
--
作者:
BELKNAP, WM;DIETSCHY, JM

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虽然体重的最大相对增长发生在胎儿生命的最后三个月,但支持这种增长的胆固醇的来源尚不确定。这些研究使用[3H]水和125i -纤维素二糖标记的低密度脂蛋白来定量大鼠胎儿体内胆固醇获得的绝对速率。初步研究表明,经静脉注射给母亲的[3H]水迅速与胎儿体内的水池平衡,并使22- 1。每微摩尔新合成的胆固醇中加入来自水池的g个H原子。给妊娠大鼠注射[3H]水后,胎儿每100克体重的固醇合成率比母鼠高数倍。然而,大坝的个别器官,如肝脏,比胎儿的合成率高得多。饲喂胆固醇抑制母体肝脏胆固醇合成时,新合成的胆固醇消失,但胎儿、胎盘和胎膜中新合成胆固醇的出现率基本没有变化。胎盘吸收低密度脂蛋白的比率是母体肝脏的三分之一,但载脂蛋白或胆固醇没有转移给胎儿。这些研究表明,大鼠胎儿在胎儿发育过程中通过局部合成从母体获得很少或没有胆固醇。此外,胎膜似乎是胎儿室中合成甾醇的重要部位。
Whereas the greatest relative increase in body mass occurs during the third trimester of fetal life, the source of the cholesterol that supports this growth is uncertain. These studies used [3H]water and 125I-cellobiose-labeled low density lipoproteins to quantitate absolute rates of cholesterol acquisition in vivo by the fetus of the rat. Preliminary studies demonstrated the [3H]water administered intravenously to the mother rapidly equilibrated with the body pool of water in the fetus and that 22-.mu.g atoms of H from the water pool were incorporated into each micromole of newly synthesized cholesterol. After administration of [3H]water to pregnant rats, the rates of sterol synthesis per 100 g of whole body weight were severalfold higher in the fetus than in the dams. Individual organs of the dam such as the liver, however, had much higher synthetic rates than those in the fetus. When maternal hepatic cholesterol synthesis was suppressed by cholesterol feeding, newly synthesized cholesterol disappeared yet there was essentially no change in the rate of appearance of newly synthesized sterol in the fetus, placenta, and fetal membranes. The placenta did take up low density lipoproteins at rates equal to about one-third of that seen in the maternal liver, but none of the apolipoprotein or cholesterol was transferred to the fetus. These studies indicate that the rat fetus receives little or no cholesterol from the mother during fetal development through local synthesis. Furthermore, the fetal membranes appear to be an important site for sterol synthesis in the fetal compartment.