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
| Autor: | Roelof Docter, H. J. Van Der Hoek, E.P. Krenning, P. G. J. Van Stralen, G. Hennemann, M. De Jong, M. E. Everts |
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| Rok vydání: | 1996 |
| Předmět: |
endocrine system
medicine.medical_specialty Triiodothyronine Reverse Liver cytology Endocrinology Diabetes and Metabolism Clinical Biochemistry Deiodinase Biology Biochemistry Ouabain chemistry.chemical_compound Endocrinology Internal medicine medicine Animals Humans Cells Cultured Triiodothyronine Biochemistry (medical) Thyroid Reverse triiodothyronine Rats medicine.anatomical_structure Liver chemistry biology.protein Propylthiouracil medicine.drug Hormone |
| Zdroj: | The Journal of Clinical Endocrinology & Metabolism. 81:244-248 |
| ISSN: | 1945-7197 0021-972X |
| DOI: | 10.1210/jcem.81.1.8550759 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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