Dietary iodide absorption in the gastrointestinal tract constitutes the first step in iodide metabolism. Since this halogen is an essential component of the thyroid, its concentrating mechanism is of considerable physiological importance. The down-regulation of NIS by high concentrations of iodide in the thyroid is related to the escape from the acute Wolff-Chaikoff effect. We have recently described NIS expression on the apical surface of the intestinal epithelium, constituting the main iodide absorption system.
This study evaluated the effect of iodide excess on intestinal NIS expression and the mechanism involved using the small intestine cell line IEC-6.
Cells treated with an excess of iodide reduced significantly the iodide uptake process which correlated with a diminution of NIS expression at the plasma membrane, but not with a maintained NIS expression in the whole protein extract NIS mRNA level was decreased by the treatment with high iodide doses. Surprisingly, no modulation on NIS promoter activity in transiently transfected IEC-6 cells was evidenced, suggesting a non transcriptional process. Evaluation of NIS protein and mRNA half-life showed that in the presence of iodide NIS protein half-life was slightly affected whereas mRNA stability was strongly reduced.
In conclusion, iodide excess down-regulates intestinal NIS function as it was similarly observed in the thyroid. The effect of high iodide concentrations regulates NIS expression through a complex mechanism that involves regulation at different levels. Although premature, these results seem to indicate that a post-transcriptional regulation is exerted on NIS by its own substrate, which could be possibly mediated by miRNAs.
