The Na+/I- symporter and biosynthesis of thyroid hormones

Abstract

The thyroid hormones are essential for the development and maturation of the central nervous system, lungs, and skeletal system, and for intermediary metabolism in virtually all tissues throughout life. Iodine is an essential constituent of these hormones, the only ones that contain it. The first step in thyroid hormone biosynthesis is the active accumulation of iodide by the thyroid follicular cells, a process mediated by the Na+/I− symporter (NIS), an integral plasma membrane glycoprotein located at the basolateral surface of these cells. In this chapter, we discuss the most recent findings on the highly complex thyroid hormone biosynthesis pathway, with an emphasis on NIS. Thyroid hormones are the only hormones whose biosynthesis takes place both intracellularly and extracellularly – in the thyroid follicular cells and at the cell/colloid interface, respectively. NIS, for its part, has emerged as a key transporter that plays a critical role not only in thyroid physiology and in the treatment of thyroid cancer with radioiodide administered after thyroidectomy, but also as the mediator of active iodide uptake in other tissues, such as lactating breast. Since the isolation of the cDNA that encodes NIS, a great deal of progress has been made in the investigation of the protein’s structure/function and regulation, and it is clear that a deeper mechanistic understanding of NIS is likely to lead to novel medical applications.