Crowe T C, Cowen N L, Loidl N M, Topliss D J, Stockigt J R, Barlow J W
Ewen Downie Metabolic Unit, Alfred Hospital, Melbourne, Victoria, Australia.
J Clin Endocrinol Metab. 1995 Jul;80(7):2233-7. doi: 10.1210/jcem.80.7.7608285.
A sensitive [125I]-T4 binding assay was used to measure serum T4-binding globulin (TBG) in 60 individuals selected on the basis of their total circulating T3 concentrations, and a relationship between TBG and circulating thyroid hormone levels in humans was confirmed. There was a significant correlation between serum TBG and T3 or free T4 index. TBG secretion and TBG messenger ribonucleic acid (mRNA) production were studied with a continuous culture of the human hepatoblastoma cell line, HepG2. Cells were maintained in serum-free media for experimental manipulations. The addition of 100 nmol/L T3 to the cell medium resulted in a time-dependent down-regulation of TBG mRNA to 33 +/- 6% (+/- SD, n = 4) of untreated control levels by 24 h. Suppression of TBG mRNA was first detectable at 8 h (57% of untreated control levels). The effect of T3 was dose-responsive, with half-maximal suppression of TBG mRNA occurring at a bioavailable T3 concentration of approximately 30 pmol/L. The effect of T3 on TBG mRNA was not caused by a change in mRNA stability. Proteins secreted by HepG2 cells bound T4 with an affinity identical to that of normal circulating TBG. Cell secretion of TBG was parallel to total protein secretion and consistent with a TBG secretion rate of 50 ng/10(6) cells per day. Variations in the concentration of secreted binding protein in the presence of T3 corresponded to the changes observed in TBG mRNA. These data show that circulating TBG concentration is negatively correlated with total serum T3 in vivo. The corresponding down-regulation observed between TBG mRNA and secreted protein in HepG2 cells suggests that this effect is the result of the action of T3 on cellular TBG mRNA synthesis.
采用灵敏的[125I]-T4结合试验，对60名根据其循环总T3浓度挑选出的个体进行血清T4结合球蛋白（TBG）检测，证实了人类体内TBG与循环甲状腺激素水平之间的关系。血清TBG与T3或游离T4指数之间存在显著相关性。利用人肝癌细胞系HepG2的连续培养研究了TBG分泌及TBG信使核糖核酸（mRNA）的产生。细胞在无血清培养基中维持用于实验操作。向细胞培养基中添加100 nmol/L T3，导致TBG mRNA在24小时内呈时间依赖性下调至未处理对照水平的33±6%（±标准差，n = 4）。TBG mRNA的抑制在8小时首次可检测到（为未处理对照水平的57%）。T3的作用具有剂量反应性，在生物可利用T3浓度约为30 pmol/L时，TBG mRNA受到半数最大抑制。T3对TBG mRNA的作用不是由mRNA稳定性变化引起的。HepG2细胞分泌的蛋白质结合T4的亲和力与正常循环TBG相同。TBG的细胞分泌与总蛋白分泌平行，且与每天50 ng/10(6)个细胞的TBG分泌率一致。在T3存在下分泌结合蛋白浓度的变化与TBG mRNA中观察到的变化相对应。这些数据表明，体内循环TBG浓度与血清总T3呈负相关。在HepG2细胞中观察到的TBG mRNA与分泌蛋白之间相应的下调表明，这种作用是T3对细胞TBG mRNA合成作用的结果。
