The sodium-iodide symporter, or NIS, is a protein embedded within cell membranes that functions as a channel to transport specific substances. Its operation is fundamental to several physiological processes by moving ions into cells where they are needed.
The Structure and Mechanism of the Sodium Iodide Symporter
The sodium-iodide symporter is a transmembrane protein, meaning it spans the entire cell membrane. In humans, it consists of 643 amino acids arranged into 13 transmembrane segments. This structure creates a specific pathway through the cell’s membrane, and its primary role is to transport iodide from the bloodstream into the cell.
This transport process is a form of secondary active transport. NIS is a “symporter,” which means it moves two different substances in the same direction across the membrane simultaneously. The symporter uses the energy from sodium ions moving down their concentration gradient to pull iodide ions into the cell against theirs. For every one iodide ion it transports, it also moves two sodium ions.
This mechanism can be likened to a revolving door that requires the force of two people (sodium ions) pushing from the outside to allow a third person (an iodide ion) to enter. The cell actively maintains a low internal sodium concentration, creating a strong electrochemical gradient that drives this process. While most prominent in the thyroid gland, NIS is also found in the salivary glands, stomach lining, and lactating mammary glands.
Essential Function in Thyroid Hormone Production
The primary physiological purpose of the sodium-iodide symporter is to initiate the production of thyroid hormones. By actively transporting iodide into thyroid follicular cells, NIS concentrates this element to levels many times higher than those found in the blood. This accumulation of iodide is the first step in synthesizing thyroxine (T4) and triiodothyronine (T3).
Once inside the thyroid cell, the iodide is moved to the apical membrane where it is oxidized and attached to a large protein called thyroglobulin. This process, known as organification, creates the foundational molecules that will become T3 and T4. These hormones are then stored within the thyroid gland and released into the bloodstream as needed to regulate the body’s metabolism.
Thyroid hormones are necessary for normal growth, brain development, and the regulation of metabolic rate in nearly all tissues. They influence everything from heart rate and body temperature to the speed at which the body uses energy. Without the initial iodide uptake facilitated by NIS, the cascade of thyroid hormone synthesis would be halted, demonstrating the protein’s role in maintaining metabolic balance.
Implications of NIS Dysfunction
When the sodium-iodide symporter does not function correctly, it primarily affects thyroid hormone production from birth. This dysfunction is often rooted in genetic mutations within the SLC5A5 gene, which provides the blueprint for the NIS protein. These mutations can result in a non-functional symporter, leading to a condition known as an iodide transport defect (ITD).
ITD is a form of dyshormonogenic congenital hypothyroidism, an autosomal recessive disorder where the thyroid gland is present but cannot produce hormones effectively. Some mutations prevent the NIS protein from embedding correctly into the cell membrane, while others alter its three-dimensional shape, impairing its ability to bind and transport iodide. In either case, the thyroid follicular cells cannot accumulate the needed iodide.
The resulting deficiency in thyroid hormones from birth can lead to severe developmental issues if not addressed promptly. This lack of hormones impairs both physical growth and cognitive development. The body attempts to compensate for low hormone levels by increasing the production of thyroid-stimulating hormone (TSH), which can cause the thyroid gland to enlarge, a condition known as a goiter.
Leveraging NIS in Medical Treatment and Imaging
The specific action of the sodium-iodide symporter is used for both diagnosing and treating certain thyroid conditions. Because NIS actively pulls iodide into thyroid cells, it can be exploited to deliver radioactive forms of iodine directly to the thyroid gland. This targeted approach uses radioactive iodine, most commonly iodine-131 (I-131).
For diagnostic purposes, small, harmless doses of radioactive iodine are administered. The NIS proteins in the thyroid gland take up the radioactive substance just as they would normal iodine. This allows physicians to perform scintigraphic imaging, creating a visual map of the thyroid that can reveal its size, shape, and functional activity.
For therapeutic uses, larger doses of I-131 are administered. This approach is effective for treating hyperthyroidism (an overactive thyroid) or certain types of thyroid cancer. The NIS in the overactive or cancerous thyroid cells concentrates the radioactive iodine, which then destroys the targeted cells with minimal damage to surrounding healthy tissue. This targeted radiation therapy has been an effective treatment for decades.