Sodium Iodide Symporter (NIS) and Thyroid
Christine Spitzweg1, John C. Morris2
Department of Internal Medicine II, Klinikum Grosshadern, Ludwig-Maximilians-University Munich, Germany1, and Division of Endocrinology, Mayo Clinic & Medical School, 200 First Street, Rochester, MN 55905, USA2
Sodium Iodide Symporter, Sodium iodide symporter gene, thyroid
Active transport of iodide into the thyroid gland is a crucial and rate-limiting step in the biosynthesis of thyroid hormones which play an important role in the metabolism, growth and maturation of a variety of organ systems, in particular the nervous system1. Although, iodide transport into the thyroid gland has been known for decades to be mediated by a specific sodium-dependent iodide transporter located at the basolateral membrane of thyroid follicular cells, the sodium iodide symporter (NIS) gene was cloned only five years ago2,3. NIS co-transports two sodium ions along with one iodide ion, with the transmembrane sodium gradient serving as the driving force for iodide uptake. This sodium gradient, providing the energy for this transfer, is generated by the ouabain-sensitive Na+/K+-ATPase. NIS-mediated iodide transport is therefore inhibited by the Na+/K+-ATPase inhibitor ouabain as well as by the competitive inhibitors thiocyanate and perchlorate1. Following active transport across the basolateral membrane, iodide is translocated across the apical membrane by pendrin, the PDS gene product, which is a chloride/iodide transporter4-8 (Figure 1). Iodide is then organified in a complex reaction including oxidation catalyzed by thyroid peroxidase (TPO) and incorporation into tyrosyl residues along the thyroglobulin (Tg) backbone. The thyroid hormones T3 and T4 are synthesized by coupling of two iodotyrosine residues and stored in the colloid. All of these steps are stimulated by pituitary-derived thyroid stimulating hormone (TSH), which interacts with the TSH receptor at the basolateral membrane of thyroidal cells, through the cAMP pathway (Figure 1)1.