Windler E E, Kovanen P T, Chao Y S, Brown M S, Havel R J, Goldstein J L
J Biol Chem. 1980 Nov 10;255(21):10464-71.
Hepatic catabolism of lipoproteins containing apolipoproteins B or E is enhanced in rats treated with pharmacologic doses of 17 alpha-ethinyl estradiol. Liver membranes prepared from these rats exhibit an increased number of receptor sites that bind 125I-labeled human low density lipoproteins (LDL) in vitro. In the present studies, this estradiol-stimulated hepatic receptor was shown to recognize the following rat lipoproteins: LDL, very low density lipoproteins obtained from liver perfusates (hepatic VLDL), and VLDL-remnants prepared by intravenous injection of hepatic VLDL into functionally eviscerated rats. The receptor also recognized synthetic lamellar complexes of lecithin and rat apoprotein E as well as canine high density lipoproteins containing apoprotein E (apo E-HDLc). It did not recognize human HDL or rat HDL deficient in apoprotein E. Much smaller amounts of this high affinity binding site were also found on liver membranes from untreated rats, the number of such sites increasing more than 10-fold after the animals were treated with estradiol. Each of the rat lipoproteins recognized by this receptor was taken up more rapidly by perfused livers from estrogen-treated rats. In addition, enrichment of hepatic VLDL with C-apoproteins lowered the ability of these lipoproteins to bind to the estradiol-stimulated receptor and diminished their rate of uptake by the perfused liver of estrogen-treated rats, just as it did in normal rats. The current data indicate that under the influence of pharmacologic doses of estradiol the liver of the rat contains increased amounts of a functional lipoprotein receptor that binds lipoproteins containing apoproteins B and E. This hepatic lipoprotein receptor appears to mediate the uptake and degradation of lipoproteins by the normal liver as well as the liver of estradiol-treated rats. The hepatic receptor bears a close functional resemblance to the LDL receptor previously characterized on extrahepatic cells.
用药理剂量的17α-乙炔雌二醇处理的大鼠，含载脂蛋白B或E的脂蛋白的肝脏分解代谢增强。从这些大鼠制备的肝细胞膜在体外显示出结合125I标记的人低密度脂蛋白（LDL）的受体位点数量增加。在本研究中，这种雌二醇刺激的肝受体被证明能识别以下大鼠脂蛋白：LDL、从肝脏灌流液中获得的极低密度脂蛋白（肝VLDL）以及通过将肝VLDL静脉注射到功能去脏大鼠体内制备的VLDL残粒。该受体还能识别卵磷脂和大鼠载脂蛋白E的合成层状复合物以及含载脂蛋白E的犬高密度脂蛋白（apo E-HDLc）。它不能识别缺乏载脂蛋白E的人HDL或大鼠HDL。在未处理大鼠的肝细胞膜上也发现了数量少得多的这种高亲和力结合位点，在用雌二醇处理动物后，这些位点的数量增加了10倍以上。这种受体识别的每种大鼠脂蛋白都被雌激素处理大鼠的灌流肝脏更快地摄取。此外，用C-载脂蛋白富集肝VLDL降低了这些脂蛋白与雌二醇刺激受体结合的能力，并降低了它们被雌激素处理大鼠的灌流肝脏摄取的速率，就像在正常大鼠中一样。目前的数据表明，在药理剂量的雌二醇影响下，大鼠肝脏中含有增加量的功能性脂蛋白受体，该受体能结合含载脂蛋白B和E的脂蛋白。这种肝脂蛋白受体似乎介导了正常肝脏以及雌二醇处理大鼠肝脏对脂蛋白的摄取和降解。肝受体在功能上与先前在肝外细胞中鉴定的LDL受体非常相似。
