Identification and evaluation of constitutively active thyroid stimulating hormone receptor mutations.

Thyroid stimulating hormone receptor (TSHR) is a guanine nucleotide-binding protein-coupled seven-transmembrane-domain receptor that controls the differentiation, growth, and function of the thyroid gland through stimulation of adenylyl cyclase and phospholipase C pathways. Thyroid stimulating hormone (TSH) is the main TSHR ligand, and unliganded receptor remains silent due to the interaction of its large extracellular domain with the extracellular loops of the serpentine. The TSHR gene is highly mutagenic and constitutively active mutations have been extensively described.