Thyrotropin receptor (TSHR) (TSHR)

The Thyrotropin receptor (TSHR) is a G protein-coupled receptor (GPCR) predominantly located on the plasma membrane of thyroid follicular cells (UniProt P16473). It is the primary regulator of thyroid function, mediating the effects of pituitary-derived Thyroid-Stimulating Hormone (TSH) to stimulate iodine uptake and the synthesis of thyroid hormones T3 and T4 (StatPearls, 'Physiology, Thyroid Stimulating Hormone'). In autoimmune conditions like Graves' disease, TSHR becomes the target of stimulatory autoantibodies (TRAbs) that mimic TSH, leading to constitutive receptor activation and clinical hyperthyroidism (PubMed, PMID: 30124804). TSHR is also critically involved in Thyroid Eye Disease (TED), where it is co-expressed and exhibits signaling crosstalk with the Insulin-like Growth Factor 1 Receptor (IGF-1R) on orbital fibroblasts (NEJM, PMID: 28467868). While clinical management often involves antithyroid drugs that inhibit downstream hormone production, direct therapeutic targeting of TSHR includes the use of recombinant TSH for diagnostic imaging and the development of monoclonal antibodies, such as K1-70, designed to neutralize the binding of pathogenic autoantibodies (ClinicalTrials.gov, NCT02904330).

Other names

Thyroid-stimulating hormone receptorTSH receptorLGR3hTSHR-I

Recombinant human TSH (Thyrotropin alfa) acts as a direct agonist to stimulate iodine uptake and thyroglobulin release; antithyroid drugs like Methimazole inhibit the synthesis of thyroid hormones downstream of the receptor, while investigational antibodies like K1-70 directly bind the receptor to block stimulatory autoantibodies.