Resistance to thyrotropin (TSH) (RTSH; defined by elevated TSH and a normal or hypoplastic thyroid gland) can be caused by mutations in genes encoding the TSH receptor and PAX8, and it has been linked to a locus on chromosome 15.
In vitro effects of the mutations on cAMP production and TSH binding were investigated in COS7 cells. cAMP production was evaluated by transfecting a cAMP response element (CRE)-luciferase reporter with pSVL-TSHR and pSVK3-GNAS vectors.
Naturally occurring activating and inactivating mutations of the thyrotropin receptor (TSHR) were found as a molecular cause of diseases in patients suffering from non-autoimmune hyperthyroidism and syndromes of thyrotropin resistance, respectively.