Transport and metabolism of iodothyronines in cultured human hepatocytes
Journal of Clinical Endocrinology and Metabolism , Volume 77 - Issue 1 p. 139- 143
Thyroid hormone uptake into cultured human hepatocytes was studied using measurement of cell-associated radioactivity of radioiodinated thyroid hormones after 10-min incubation in culture medium with 0.5% BSA. Furthermore, 20-h incubations were performed to study transport and further intracellular metabolism. The results indicate the presence of saturable active uptake systems for T4, T3, and rT3, as addition of the unlabeled hormone (1, 5, and 2 μmol/L, respectively) to the medium resulted in a decrease in cell-associated radioactivity of 20-30%. Inhibition was also achieved after 30-min preincubation with fructose (10 mmol/L), which induces a decrease in intracellular ATP or ouabain (0.5 mmol/L), indicating energy dependence and the necessity for a sodium gradient for at least part of the transport process, respectively. After 20-h incubation, iodide production was inhibited in the presence of ouabain (0.5 mmol/L), propylthiouracil (100 μmol/L), or a monoclonal antibody (81-1A1-10; ascites dilution, 1:200) directed against thyroid hormone transport systems in rat hepatocytes. These data indicate that there is a high degree of similarity between the properties of the uptake process and subsequent conversion of thyroid hormones in human and rat hepatocytes, although the rates of uptake and conversion are lower in human hepatocytes. Furthermore, regulation of thyroid hormone uptake at the level of the plasma membrane may also be operative in human hepatocytes.
|Journal of Clinical Endocrinology and Metabolism|
|Organisation||Department of Nuclear Medicine|
de Jong, M, Visser, T.J, Bernard, B.F, Docter, R, Vos, R.A, Hennemann, G, & Krenning, E.P. (1993). Transport and metabolism of iodothyronines in cultured human hepatocytes. Journal of Clinical Endocrinology and Metabolism, 77(1), 139–143. doi:10.1210/jc.77.1.139