Department of Clinical Chemistry and University Medical Center Rotterdam, Rotterdam, the Netherlands.
Department of Internal Medicine; University Medical Center Rotterdam, Rotterdam, the Netherlands.
Department of Academic Center for Thyroid Diseases; Erasmus MC, University Medical Center Rotterdam, Rotterdam, the Netherlands.
背景 与甲状腺激素 T3 和 T4 相比，甲状腺激素分布蛋白 (THDP)、甲状腺素结合球蛋白 (TBG)、白蛋白和甲状腺素运载蛋白与甲状腺激素代谢物的结合特征大多缺乏。在这项研究中，我们确定了甲状腺激素代谢物与 THDP 的分布和结合亲和力，这对于充分解释甲状腺激素代谢物浓度很重要。方法通过琼脂凝胶电泳测定125I-3,3'-T2、-T3、-rT3、-TA3和-TA4在TBG、转甲状腺素蛋白和白蛋白中的分布。TBG 和转甲状腺素蛋白对 T0、3-T1、3,5-T2、3,3'-T2、T3、rT3、T4、TA3 和 TA4 的亲和力等级顺序 (IC50) 用放射性配体竞争结合测定法确定. 在健康受试者中，血清 TBG 与 使用多元线性回归模型分析转甲状腺素蛋白和白蛋白与 TH 及其代谢物，并根据性别和年龄进行调整。结果虽然 T3 和 T4 主要与 TBG 结合，但我们证明 3,3'-T2 和 rT3 的主要 THDP 是白蛋白，TA3 是转甲状腺素蛋白和白蛋白，TA4 是转甲状腺素蛋白。通过放射性配体结合试验，我们发现 TBG 的亲和力排序为 T4>TA4=rT3>T3>TA3=3,3'-T2>3-T1=3,5-T2>T0（IC50 范围： 0.36 nM 至 >100 µM）和 TA4>T4=TA3>rT3>T3>3,3'-T2>3-T1>3,5-T2>T0 用于转甲状腺素蛋白（IC50 范围：0.94 nM 至 >100 µM） . TBG、转甲状腺素蛋白和白蛋白与 T0、3-T1、3,3'-T2、rT3 和 TA4 无关。结论 血清 TBG 的差异，参考区间内的转甲状腺素蛋白和白蛋白浓度不影响 T0、3-T1、3,3'-T2、rT3 和 TA4 的血清浓度。THDP 之间的甲状腺激素代谢物分布不同于主要与 TBG 结合的 T4 和 T3。我们的研究结果对于充分解释（病理）生理学中的 TH 代谢具有潜在的临床意义。
Background In contrast to the thyroid hormones T3 and T4, binding characteristics of the thyroid hormone distributor proteins (THDP), thyroxine-binding globulin (TBG), albumin and transthyretin in relation to thyroid hormone metabolites are mostly lacking. In this study, we determined the distribution and binding affinity of thyroid hormone metabolites to THDP, which is important for adequate interpretation of thyroid hormone metabolite concentrations. Methods Distribution of 125I-3,3’-T2, -T3, -rT3, -TA3 and -TA4 to TBG, transthyretin and albumin was determined by agar gel electrophoresis. The rank order of affinity (IC50) of TBG and transthyretin to T0, 3-T1, 3,5-T2, 3,3’-T2, T3, rT3, T4, TA3 and TA4 was determined with a radioligand, competitive binding assay. In healthy subjects, associations of serum TBG, transthyretin and albumin with TH and its metabolites were analyzed using multiple linear regression models, adjusted for sex and age. Results While T3 and T4 are predominantly bound to TBG, we demonstrated that the predominant THDP of 3,3’-T2 and rT3 is albumin, of TA3 is transthyretin and albumin and of TA4 is transthyretin. With the radioligand binding assay, we showed that the rank order of affinity was T4>TA4=rT3>T3>TA3=3,3’-T2>3-T1=3,5-T2>T0 for TBG (IC50-range: 0.36 nM to >100 µM) and TA4>T4=TA3>rT3>T3>3,3’-T2>3-T1>3,5-T2>T0 for transthyretin (IC50-range: 0.94 nM to >100 µM). TBG, transthyretin and albumin were not associated with T0, 3-T1, 3,3’-T2, rT3 and TA4. Conclusions Differences in serum TBG, transthyretin and albumin concentrations within the reference interval do not influence serum concentrations of T0, 3-T1, 3,3’-T2, rT3 and TA4. Distribution of thyroid hormone metabolites between THDP differs from T4 and T3, which predominantly bind to TBG. The results from our study have potential clinical importance for adequate interpretation of TH metabolism in (patho)physiology.
