The TSHR gene provides instructions for making a protein, known as a receptor, that attaches (binds) to a hormone called thyroid stimulating hormone (TSH). This receptor spans the membrane of certain cells (called follicular cells) in the thyroid gland, a butterfly-shaped tissue in the lower neck. A large part of the receptor sites on the outer surface of the cell (extracellular), and a small portion is retained inside the cell (intracellular). Thyroid stimulating hormone binds to the extracellular portion of the receptor like a key fitting into a lock, activating a series of reactions that control the development of the thyroid gland and its functions. Among its functions, the thyroid gland produces iodine-containing hormones (thyroid hormones), which help regulate growth, brain development, and the rate of chemical reactions in the body (metabolism).
The encoded protein is a receptor for thyrotropin and thyrostimulin, and its activity is mediated by adenylate cyclase. Defects in this gene are a cause of several types of hyperthyroidism.
TSHR gene mutations can cause disorders associated with hyperthyroidism. These mutations change one of the amino acids used to make the thyroid stimulating hormone receptor. As a result, the receptor is continuously activated and overstimulates the production of thyroid hormones. TSHR gene mutations can lead to an enlarged thyroid gland (goiter) and symptoms of hyperthyroidism, such as a rapid heartbeat. Hyperthyroidism that is present from birth is called nonautoimmune congenital hyperthyroidism (or sporadic toxic thyroid hyperplasia). The onset of hyperthyroidism that begins in childhood or adulthood is known as nonautoimmune autosomal dominant hyperthyroidism (or hereditary toxic thyroid hyperplasia).