Post-transcriptional regulation of the sodium/iodide symporter by thyrotropin

The Na+/I- symporter (NIS) is a key plasma membrane glycoprotein that media tes active I- transport in the thyroid gland (Dai, G., Levy, O., and Carras co, N. (1996) Nature 379, 458-460), the first step in thyroid hormone bioge nesis, Whereas relatively little is known about the mechanisms by which thy rotropin (TSH), the main hormonal regulator of thyroid function, regulates NIS activity, post-transcriptional events have been suggested to play a rol e (Kaminsky, S. M., Levy, O., Salvador, C., Dai, G., and Carrasco, N. (1994 ) Proc. Natl. Acad. Sci. U.S.A. 91, 3789-3793), Here we show that TSH induc es de novo NIS biosynthesis and modulates the long NIS half-life (similar t o5 days). In addition, we demonstrate that TSH is required for NIS targetin g to or retention in the plasma membrane. We further show that NIS is a pho sphoprotein and that TSH modulates its phosphorylation pattern. These resul ts provide strong evidence of the major role played by post-transcriptional events in the regulation of NIS by TSH. Beyond their inherent interest, it is also of medical significance that these TSH-dependent regulatory mechan isms may be altered in the large proportion of thyroid cancers in which NIS is predominantly expressed in intracellular compartments, instead of being properly targeted to the plasma membrane.