van Stralen P G, van der Hoek H J, Docter R, de Jong M, Krenning E P, Everts M E, Hennemann G
Department of Internal Medicine III, Erasmus University Medical School, Rotterdam, The Netherlands.
J Clin Endocrinol Metab. 1996 Jan;81(1):244-8. doi: 10.1210/jcem.81.1.8550759.
The uptake and metabolism of T3 and rT3 was studied in human liver-derived HepG2 cells. The results showed a saturable, time-dependent, and ouabain-sensitive increase in nuclear bound T3. The effects of ouabain (0.5 mmol/L) and unlabeled T3 (10 nmol/L and 10 mumol/L) were much more pronounced at the nuclear level, suggesting the presence of a nonspecific component in total cellular binding. Nuclear binding of rT3 remained below the detection limit in all experiments. Comparison of rT3 metabolism in HepG2 cells and primary cultures of rat hepatocytes showed an approximately 10-fold lower iodide production in HepG2 cells. Iodide production was decreased in the presence of ouabain and almost absent in the presence of propylthiouracil (100 mumol/L). Our data confirmed the presence of a carrier-mediated uptake system for both T3 and rT3. Metabolism data indicated functional type I deiodinase activity in HepG2 cells, the presence of glucuronidating enzymes, and the absence of thyroid hormone sulfotransferase activity. Based on these data, we propose that HepG2 cells provide an appropriate model for thyroid hormone handling by human liver. In addition, we suggest that in human liver sulfation of thyroid hormone, and therefore deiodination of T3 is of only minor importance.
在人肝脏来源的HepG2细胞中研究了T3和反T3（rT3）的摄取和代谢。结果显示，核结合T3呈饱和、时间依赖性且对哇巴因敏感的增加。哇巴因（0.5 mmol/L）和未标记的T3（10 nmol/L和10 μmol/L）在核水平的作用更为明显，提示总细胞结合中存在非特异性成分。在所有实验中，rT3的核结合均低于检测限。比较HepG2细胞和大鼠肝细胞原代培养物中rT3的代谢发现，HepG2细胞中的碘生成量约低10倍。在哇巴因存在的情况下碘生成减少，在丙硫氧嘧啶（100 μmol/L）存在时几乎不存在碘生成。我们的数据证实了T3和rT3均存在载体介导的摄取系统。代谢数据表明HepG2细胞中存在功能性I型脱碘酶活性、葡糖醛酸化酶，且不存在甲状腺激素硫酸转移酶活性。基于这些数据，我们提出HepG2细胞为人类肝脏处理甲状腺激素提供了一个合适的模型。此外，我们认为在人类肝脏中，甲状腺激素的硫酸化以及因此T3的脱碘作用仅具有次要重要性。
