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在非甲状腺疾病患者血清存在的情况下,大鼠肝细胞对甲状腺素和3,5,3'-三碘甲状腺原氨酸的处理受损。

Impaired thyroxine and 3,5,3'-triiodothyronine handling by rat hepatocytes in the presence of serum of patients with nonthyroidal illness.

作者信息

Vos R A, De Jong M, Bernard B F, Docter R, Krenning E P, Hennemann G

机构信息

Department of Internal Medicine III, University Hospital Dijkzigt, Erasmus University, Rotterdam, The Netherlands.

出版信息

J Clin Endocrinol Metab. 1995 Aug;80(8):2364-70. doi: 10.1210/jcem.80.8.7629231.

DOI:10.1210/jcem.80.8.7629231
PMID:7629231
Abstract

In systemic nonthyroidal illness (NTI), peripheral production of T3 from T4 is decreased, resulting in a decreased serum T3 concentration. We investigated whether factors in serum of NTI patients may play a role in this energy-saving adaptation mechanism. Metabolism of T4 and T3 by rat hepatocytes in primary culture was measured in the presence of 10% serum of normal subjects or of patients with NTI and related to the severity of disease. Patients with NTI were grouped according to serum thyroid hormone abnormalities: group I, serum rT3, T3, and T4 normal; group III, rT3 elevated, T3 decreased, T4 normal; group IV, rT3 elevated, T3 and T4 decreased. Compared with metabolism in the presence of normal serum, metabolism of T4 and to a lesser extent of T3 was progressively decreased in the presence of serum of patients of groups I-IV. A decreased net deiodination of T4 and T3 (corrected for differences in free hormone concentration) without an increase in conjugated T4 and T3 (corrected for differences in free hormone concentration) was observed, similar to results in experiments with compounds inhibiting transport into the cells and not the metabolic processes (5' deiodination) per se. Deiodination of T4 in vitro was correlated with serum T3 concentration of the patient (r = 0.69). Serum of patients with NTI influences thyroid hormone handling by hepatocytes comparable to the effect of transport inhibitors and not to that of the 5'-deiodinase inhibitor propylthiouracil, suggesting that decreased thyroid hormone transport over the cell membrane may play a role in lowered T3 production in NTI.

摘要

在全身性非甲状腺疾病(NTI)中,外周由T4生成T3的过程减少,导致血清T3浓度降低。我们研究了NTI患者血清中的因素是否可能在这种节能适应机制中发挥作用。在存在10%正常受试者或NTI患者血清的情况下,测量原代培养的大鼠肝细胞对T4和T3的代谢,并与疾病严重程度相关联。NTI患者根据血清甲状腺激素异常情况分组:I组,血清反T3(rT3)、T3和T4正常;III组,rT3升高,T3降低,T4正常;IV组,rT3升高,T3和T4降低。与正常血清存在时的代谢相比,I - IV组患者血清存在时T4的代谢以及程度较轻的T3的代谢逐渐降低。观察到T4和T3的净脱碘作用降低(校正游离激素浓度差异),而结合型T4和T3没有增加(校正游离激素浓度差异),这与用抑制细胞转运而非代谢过程(5'脱碘)本身的化合物进行实验的结果相似。体外T4的脱碘作用与患者的血清T3浓度相关(r = 0.69)。NTI患者的血清对肝细胞处理甲状腺激素的影响与转运抑制剂的作用相当,而与5'-脱碘酶抑制剂丙硫氧嘧啶的作用不同,这表明细胞膜上甲状腺激素转运减少可能在NTI中T3生成降低中起作用。

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