Schematic diagram of a follicular cell, illustrating the steps involved in thyroid hormone synthesis. TSH receptor (TSHR) bound to TSH stimulates iodide transport into the thyroid gland by the sodium iodide symporter (NIS). Subsequently, iodide is oxidised by hydrogen peroxide, generated by the recently discovered NADPH oxidase system (ThOX) and bound to tyrosine residues in thyroglobulin (TG) to form iodotyrosine (iodide organification). Some of these hormonally inactive iodotyrosine residues (monoiodotyrosine and diiodotyrosine) couple to form the hormonally active iodothyronines, T4 and T3. Thyroid peroxidase (TPO) catalyses the oxidation, organification, and coupling reactions. The exact function of pendrin, a chloride-iodide transporter, in thyroid hormone synthesis is as yet unknown but it is thought to transport iodide into the colloid from the thyrocyte. Defects in any of these steps lead to dyshormonogenesis, which manifests clinically as congenital hypothyroidism with goitre.
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