Induction of follicle formation in long-term cultured normal human thyroidcells treated with thyrotropin stimulates iodide uptake but not sodium/iodide symporter messenger RNA and protein expression

Iodide uptake by the sodium/iodide symporter (NIS) in thyrocytes is essenti al for thyroid hormone production. Reduced NIS activity has been reported i n thyroid diseases, including thyroid cancer and congenital hypothyroidism. The study of iodide uptake in thyrocytes has been limited by the availabil ity of appropriate in vitro models, A new culture technique was recently de veloped that allows normal human thyroid primary culture cells to grow as m onolayer cells and express differentiated functions for more than 3 months. We used this technique to study the effect of follicle formation and TSH o n iodide uptake in these cells. Iodide uptake by the cells grown in monolay er was very low. Follicle formation was induced from monolayer cells, and e lectron micrographs demonstrated cell polarity in the follicles. No signifi cant increase in iodide uptake was observed after TSH treatment of cells in monolayer or when follicle formation was induced without TSH. TSH stimulat ion of follicles, however, significantly increased iodide uptake (similar t o4.4-fold; P<0.001). Compared with iodide uptake in monolayers, the combina tion of follicle formation and TSH treatment stimulated iodide uptake syner gistically to 12.0-fold (P<0.001). NIS messenger RNA (mRNA) and protein lev els were almost the same in both monolayer cells and follicles. TSH treatme nt of monolayers and follicles produced significant (P<0.05) stimulation of mRNA (<similar to>4.8- and 4.3-fold respectively) and protein (similar to6 .8- and 4.9-fold respectively). TSH stimulated NIS protein levels in both m onolayer and follicles, however, stimulation of functional iodide uptake wa s only seen with TSH stimulation of follicles. The function of NIS may invo lve post-transcriptional events, such as intracellular sorting, membrane lo calization of NIS or another NIS regulatory factor. Polarized functions, su ch as iodide efflux into follicular lumina, may also contribute to the incr eased iodide concentration after follicle formation.