Thyroid Stimulating Hormone Receptor

The growth and function of the thyroid are controlled by thyrotropin through activation of the thyroid-stimulating hormone (TSH) receptor.36 Mutations in TSH receptors are found in approximately 30% of all human thyroid adenomas.37 In recent years, various constitutively active mutations within the TSH receptor were identified and shown to be associated with continuous stimulation of the cAMP pathway, causing hyperthyroidism and thyroid hyperplasia. Similarly, in Graves' disease, autoantibodies mimic the action of thyrotropin,38 leading to activation of this receptor. Thyroid carcinogenesis, however, is associated with constitutively activating receptor mutants and an activating mutation within the Ras gene, suggesting that both the Ras and TSH mutations act synergistically to cause the tumor phenotype in some differentiated thyroid carcinomas.39

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