Sodium/iodide cotransporter

Sodium/Iodide Symporter (NIS) is an integral membrane glycoprotein that mediates the active transport of iodide (I-) into thyroid follicular cells, the first step in the synthesis of thyroid hormones. This symporter is also expressed in other tissues, such as salivary glands, gastric mucosa, and lactating mammary glands, albeit its function in these tissues is less understood. The NIS uses the sodium gradient maintained by the Na+/K+-ATPase pump to co-transport iodide ions into the cell against their concentration gradient, a process crucial for thyroid hormone production.

Function

The primary function of the NIS is to concentrate iodide in the thyroid gland, which is essential for the synthesis of thyroid hormones, thyroxine (T4) and triiodothyronine (T3). These hormones are critical regulators of metabolism, growth, and development. The NIS actively transports two sodium ions (Na+) along with one iodide ion (I-) into the thyroid follicular cells from the bloodstream, utilizing the sodium gradient as the driving force.

Structure

The NIS is a transmembrane protein that spans the plasma membrane 13 times, creating a pore through which ions can be transported. Its exact molecular structure is yet to be fully elucidated, but it is known to have a large extracellular domain, which is thought to be involved in iodide recognition and binding.

Regulation

The activity of the NIS is regulated by thyroid-stimulating hormone (TSH), which is secreted by the pituitary gland. TSH stimulates the transcription and expression of the NIS gene, thereby increasing iodide uptake into the thyroid gland. Other factors, such as iodide concentration, also modulate NIS expression and function.

Clinical Significance

Alterations in NIS function can lead to various thyroid disorders. Reduced NIS expression or activity can result in insufficient thyroid hormone production, leading to hypothyroidism. Conversely, excessive NIS activity can contribute to hyperthyroidism. The NIS is also a target for radioactive iodide treatment in thyroid cancer, as cancerous thyroid cells expressing NIS can accumulate radioactive iodide, leading to their destruction.

Research

Research on the NIS has expanded our understanding of thyroid physiology and pathophysiology. It has also opened avenues for novel therapeutic strategies in treating thyroid diseases and certain types of breast cancer, as NIS expression has been observed in breast tissues.