Influx of thyroid hormones into rat liver in vivo. Differential availability of thyroxine and triiodothyronine bound by plasma proteins.
Influx of thyroid hormones into rat liver in vivo. Differential availability of thyroxine and triiodothyronine bound by plasma proteins.
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甲状腺激素流入大鼠体内肝脏。
DOI：
10.1172/jci109865
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发表时间：
1980
期刊：
影响因子：
--
通讯作者：
L. Mietus
中科院分区：
文献类型：
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作者：
W. Pardridge;L. Mietus
采用组织取样-门静脉注射技术研究了麻醉大鼠[(125)I]甲状腺素（T(4)）和[(125)I]三碘甲状腺原氨酸（T(3)）在肝脏中的转运。该方法允许研究人血清中血浆蛋白对T(4)或T(3)单向流入肝细胞的影响。门静脉注射一剂林格氏液后，T(3)和T(4)的单向清除率分别为77+/-2%和43+/-2%。T(4)或T(3)的细胞膜运输是不饱和的，因为50-muM浓度的未标记激素对运输没有影响。在体外，添加浓度为1、5或10 g/100 ml的牛白蛋白能结合98%的T(4)或T(3)，但对体内T(3)或T(4)的转运没有显著影响。相反，10%的兔T(3)或T(4)特异性抗血清完全消除了甲状腺激素进入肝脏的细胞内分布。在含有白蛋白和甲状腺激素结合前白蛋白（TBPA）的大鼠血清存在的情况下，血浆总T(4)和总T(3)分别有18%和81%可在体内运输。正常人血清中含有白蛋白、TBPA和甲状腺激素结合球蛋白（TBG），可用于运输的激素比例在T(4)中为11%，在T(3)中为72%。注射孕妇或服用避孕药的志愿者的血清后，转运到肝脏的激素比例在T(4)中为4%（但这与零没有显著差异），在T(3)中为54%。这些数据表明：(a) T(4)和T(3)通过肝细胞膜的机制可能是自由扩散。(b)白蛋白结合的T(4)或T(3)被肝脏自由清除，约50%的tbg结合的T(3)被运输，但很少（如果有的话）tbpa结合的T(4)或tbg结合的T(4)被肝细胞清除。(c)尽管T(4)的白蛋白结合部分大大超过游离（可透析）部分，但这两个部分都与现有TBA或TBG水平呈负相关；因此，体外游离T(4)的测量有望准确反映体内可运输的T(4)。相反，tbg结合的T(3)很容易在体内运输；因此，有人提出，体外游离T(3)的测量不能可靠地预测体内可转运到肝脏的T(3)的比例。
The transport of [(125)I]thyroxine (T(4)) and [(125)I]triiodothyronine (T(3)) into liver was investigated with a tissue sampling-portal vein injection technique in the anesthetized rat. The method allows the investigation of the effects of plasma proteins in human serum on the unidirectional influx of T(4) or T(3) into liver cells. The percent extraction of unidirectional clearance of T(3) and T(4) was 77+/-2% and 43+/-2%, respectively, after portal injection of a bolus of Ringer's solution. Cell membrane transport of T(4) or T(3) was nonsaturable because 50-muM concentrations of unlabeled hormone had no effect on transport. The addition of bovine albumin in concentrations of 1, 5, or 10 g/100 ml bound >98% of T(4) or T(3) in vitro, but had no significant effect on T(3) or T(4) transport in vivo. Conversely, 10% rabbit antisera specific for T(3) or T(4), completely abolished the intracellular distribution of thyroid hormone into liver. In the presence of rat serum, which contains albumin and thyroid hormone binding pre-albumin (TBPA), 18 and 81% of total plasma T(4) and T(3), respectively, were available for transport in vivo. The fraction of hormone available for transport in the presence of normal human serum, which contains albumin, TBPA, and thyroid hormone binding globulin (TBG) was 11% for T(4) and 72% for T(3). The fraction of hormone transported into liver after injection of serum obtained from pregnant or birth control pilltreated volunteers was 4% for T(4) (but this was not significantly different from zero) and 54% for T(3). THESE DATA SUGGEST: (a) The mechanism by which T(4) and T(3) traverse the liver cell membrane is probably free diffusion. (b) Albumin-bound T(4) or T(3) is freely cleared by liver, approximately 50% of TBG-bound T(3) is transported, but little, if any, of TBPA-bound T(4) or TBG-bound T(4) is cleared by liver cells. (c) Although the albumin-bound fraction of T(4) greatly exceeds the free (dialyzable) moiety, the two fractions are both inversely related to the existing TBA or TBG level; therefore, in vitro measurements of free T(4) would be expected to accurately reflect what is available for transport in vivo. Conversely, TBG-bound T(3) is readily transported in vivo; therefore, it is proposed that in vitro measurements of free T(3) do not reliably predict the fraction of T(3) available for transport into liver in vivo.