Uptake and metabolism of 3,5,3'-triiodothyronine and 3,3',5'-triiodothyronine by human liver-derived cells: HepG2 cells as a model for thyroid hormone handling by human liver

The uptake and metabolism of T-3 and rT(3) was studied in human liver-derived HepG2 cells. The results showed a saturable, time-dependent, and ouabain-sensitive increase in nuclear bound T-3. The effects of ouabain (0.5 mmol/L) and unlabeled T-3 (10 nmol/L and 10 mu mol/L) were much more pronounced at the nuclear level, suggesting the presence of a nonspecific component in total cellular binding. Nuclear binding of rT(3) remained below the detection limit in all experiments. Comparison of rT(3) 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 mu mol/L). Our data confirmed the presence of a carrier-mediated uptake system for both T-3 and rT(3). 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 T-3 is of only minor importance.