Hossner K L, Billiar R B
Biochim Biophys Acta. 1979 Jul 18;585(4):543-53. doi: 10.1016/0304-4165(79)90187-9.
Plasma kinetics and liver metabolism of iodinated human corticosteroid-binding protein have been studied in ovariectomized female rats. 125I-labeled human corticosteroid-binding globulin prepared by a modified chloramine T reaction was shown to be physically intact and biologically active. Intravenously injected 125I-labeled human corticosteroid-binding globulin was shown to give a complex clearance pattern from the plasma, with half-lives of 7.5 and 51 min. Estrogen injections had no effect on plasma clearance rate. Direct involvement of liver plasma membrane receptors for asialoglycoproteins in 125I-labeled human corticosteroid-binding globulin metabolism was demonstrated in vivo and in vitro using asialofetuin as a competitive inhibitor. 125I labeled human asialo-corticosteroid-binding globulin was cleared from the plasma with a half-life of less than 1 min, while the simultaneous injection of 5 mg asialofetuin maintained the circulating plasma lebels. Asialofetuin also slowed the clearance of intact 125I-labeled human corticosteroid-binding globulin from the plasma (t1/2 = 90 min). Binding of 125I-labeled human asialo-corticosteroid-binding globulin to rat liver plasma membranes in vitro was inhibited in a dose-dependent manner by asialofetuin, but not by intact human corticosteroid-binding globulin or fetuin. 125I-labeled human corticosteroid-binding globulin did not bind significantly to the membranes. It is concluded that human corticosteroid-binding globulin clearance from rat plasma is rapid and that the carbohydrate moiety of human corticosteroid-binding globulin is involved in its clearance and catabolism by the liver.
已在去卵巢的雌性大鼠中研究了碘化人皮质类固醇结合蛋白的血浆动力学和肝脏代谢。通过改良的氯胺T反应制备的125I标记的人皮质类固醇结合球蛋白在物理上是完整的且具有生物活性。静脉注射的125I标记的人皮质类固醇结合球蛋白在血浆中呈现复杂的清除模式，半衰期分别为7.5分钟和51分钟。注射雌激素对血浆清除率没有影响。使用去唾液酸胎球蛋白作为竞争性抑制剂，在体内和体外均证明了肝细胞膜上的去唾液酸糖蛋白受体直接参与125I标记的人皮质类固醇结合球蛋白的代谢。125I标记的人去唾液酸皮质类固醇结合球蛋白从血浆中的清除半衰期小于1分钟，而同时注射5mg去唾液酸胎球蛋白可维持循环血浆水平。去唾液酸胎球蛋白还减缓了完整的125I标记的人皮质类固醇结合球蛋白从血浆中的清除（t1/2 = 90分钟）。在体外，去唾液酸胎球蛋白以剂量依赖的方式抑制125I标记的人去唾液酸皮质类固醇结合球蛋白与大鼠肝细胞膜的结合，但完整的人皮质类固醇结合球蛋白或胎球蛋白则无此作用。125I标记的人皮质类固醇结合球蛋白与细胞膜无明显结合。结论是人皮质类固醇结合球蛋白从大鼠血浆中的清除很快，并且人皮质类固醇结合球蛋白的碳水化合物部分参与其在肝脏中的清除和分解代谢。
