REDUCED CLEARANCE RATE OF THYROXINE-BINDING GLOBULIN (TBG) WITH INCREASED SIALYLATION - A MECHANISM FOR ESTROGEN-INDUCED ELEVATION OF SERUM TBG CONCENTRATION
REDUCED CLEARANCE RATE OF THYROXINE-BINDING GLOBULIN (TBG) WITH INCREASED SIALYLATION - A MECHANISM FOR ESTROGEN-INDUCED ELEVATION OF SERUM TBG CONCENTRATION
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DOI：
10.1210/jcem-65-4-689
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发表时间：
1987-10-01
影响因子：
5.8
通讯作者：
REFETOFF, S
中科院分区：
文献类型：
--
作者：
AIN, KB;MORI, Y;REFETOFF, S
高雌激素状态，包括怀孕，会导致血清T4结合球蛋白(TBG)浓度增加，以及等电聚焦时具有更大阳离子迁移率的TBG分子比例增加，表明唾液酸含量更高。通过测定不同等电点TBG的体内半衰期(T1/2)，探讨唾液酸化程度与血清中TBG蓄积之间的可能因果关系。大鼠静脉注射全血清白蛋白及其主要峰，用等电点进行分离。注射后每隔一段时间采集血清样本，用放射免疫法测定血清中的总胆红素浓度，用来计算t1/2。孕妇血清中总胆红素的t1/2显著延长至17.2+-。1.2小时(平均+-SD)，而13.3.+-。1.5和12.9+-。男性和未怀孕女性的血清总胆红素浓度分别为0.9。随着阳极迁移率的增加，TBG峰II、III、IV和V的T1/2值逐渐延长，分别为11、13、15和33h。然而，从孕妇和非孕者的血清分离的IEF上相同迁移率的TBG峰具有相似的T1/2值。血清总胆红素浓度和雌激素对总胆红素清除率均无直接影响。事实上，来自遗传性TBG过剩受试者的TBG的T1/2与来自非怀孕女性或男性的TBG的T1/2没有什么不同。大鼠经雌二醇慢性处理后，对注射人TBG的清除速率无明显改变。最后，通过免疫印迹分析，纯化的但未分离的血清TBG阳极带的唾液酸化程度更高，在大鼠的循环中存活时间更长。这些结果表明，TBG的体内代谢率与其唾液酸含量有关。因此，在高雌激素状态下，唾液酸含量较高的TBG分子所占比例的增加导致血清TBG浓度的升高。
Hyperestrogenemic states, including pregnancy cause an increase in serum T4-binding globulin (TBG) concentrations and an increase in the proportion of TBG molecules with greater anodal mobility on isoelectric focusing, indicating greater sialic acid content. The possible causal relationship between the degree of sialylation and accumulation of TBG in serum was explored by measuring the in vivo half-lives (t1/2) of TBGs with different isoelectric points. TBG in unfractionated serum and its major peaks, isolated by chromatofocusing and defined by their isoelectric points on isoelectric focusing were each injected iv into rats. The resulting TBG concentrations, measured by specific RIA in serum samples obtained at intervals after injection, were used for the calculation of the t1/2. TBG in serum from a pregnant woman had a significant longer t1/2 of 17.2 .+-. 1.2 h (mean .+-. SD) compared to those of 13.3 .+-. 1.5 and 12.9 .+-. 0.9 for TBG in serum from a man and a nonpregnant woman, respectively. TBG peaks II, III, IV, and V, with increasing anodal mobility, had progressively longer t1/2 values of 11, 13, 15, and 33 h, respectively. However, TBG peaks of the same mobility on IEF isolated from serum of pregnant or nonpregnant subjects had similar t1/2 values. Neither the TBG concentration nor estrogen had a direct effect on the rate of TBG clearance. Indeed, that t1/2 of TBG from a subject with inherited TBG excess was not different from that of TBG from a nonpregnant woman or a man. Chronic treatment of rats with estradiol did not alter the rate of clearance of injected human TBG. Finally, the more heavily sialylated anodal bands of purified but unfractionated serum TBG, analyzed by Western blots, survived longer in the circulation of a rat. These results indicate that the rate of in vivo metabolism of TBG is dependent on its sialic acid content. The increased proportion of TBG molecules with higher sialic acid content thus contributes to the increase in the serum TBG concentration in hyperestrogenemic states.