Endocrine Abstracts

When cultured in serum-free conditions, primary cultures of human thyroid cells display TSH-dependent iodide uptake and organification and iodide-dependent thyroid hormone synthesis. High iodide concentrations (>1 microM) inhibit thyroid hormone synthesis but iodide (0.1 microM) is obligatory for thyroid hormone secretion into the medium. We have performed in vitro studies examining the regulation of iodide transport and organification in cells preincubated in varying concentrations of iodide. Cells were preincubated for 7 days and iodide transport, measured by uptake of 125I in the presence of 1 mM methimazole to block iodide organification, was inhibited by high iodide concentrations. This indicates that the Wolff-Chaikoff effect i.e iodide-mediated down regulation of iodide transport is occurring. If the preincubations in iodide were performed in the presence of methimazole, which blocks the enzyme thyroperoxidase, these inhibitory effects were abolished and iodide transport was maintained. Cultures preincubated in the presence of methimazole showed increased trapping of iodide with preincubation in increasing concentrations of iodide, indicating that iodide per se stimulates iodide transport. When the organification of iodide was examined, 125I incorporation into iodoprotein was lower in the cultures preincubated in high iodide. However, since the percentage of iodide incorporated into iodoprotein in these cultures was not inhibited this reduction is likely due to the decrease in trapping. In those cultures preincubated in high iodide and methimazole, there was no effect on iodide organification indicating that iodide per se has no effect on thyroperoxidase activity. We conclude that in human thyroid cell cultures, organified intermediates containing iodine, inhibit iodide transport in vitro mimicking the Wolff-Chaikoff effect observed in vivo. This effect is specific for iodide transport as iodide organification is not inhibited. Iodide per se exerts a stimulatory effect on iodide transport and does not inhibit peroxidase.