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.