Thyroid-stimulating hormone receptor (TSHR) (TSHR)

The thyroid-stimulating hormone receptor (TSHR) is a G protein-coupled receptor (GPCR) predominantly found on the surface of thyroid follicular cells, where it plays a central role in regulating thyroid function [1, 10]. Its primary biological function is to mediate the effects of thyroid-stimulating hormone (TSH), which activates signaling cascades—principally the Gs/cAMP pathway—to stimulate the synthesis and secretion of thyroid hormones T3 and T4 [1, 17]. In clinical pathology, TSHR is the primary autoantigen in Graves' disease, where it is targeted by pathogenic autoantibodies known as TSH receptor antibodies (TRAb) [4, 11]. These autoantibodies can act as agonists leading to hyperthyroidism or as antagonists causing hypothyroidism, making them critical biomarkers for diagnosis and monitoring [2, 14]. Therapeutic strategies involve the use of antithyroid medications to inhibit hormone synthesis, radioactive iodine for ablation, and emerging biological antagonists like K1-70 that directly block the receptor [4, 5]. Additionally, TSHR is a key target in Graves' ophthalmopathy due to its expression in retro-orbital tissues and its functional crosstalk with the insulin-like growth factor 1 receptor (IGF-1R) [17].

Other names

Thyrotropin receptorThyroid-stimulating hormone receptorTSH receptorLGR3Seven transmembrane helix receptor

Therapeutic modulation includes competitive antagonism of the receptor to block pathogenic autoantibody binding, allosteric inhibition of receptor signaling, and downstream suppression of thyroid hormone synthesis.