Thyroxine hormone is produced in the thyroid gland from tyrosine and iodine. Thyrotropin-releasing hormone (TRH) is produced by the hypothalamus. It stimulates the production of thyroid-stimulating hormone (TSH) in the anterior pituitary gland, which affects the thyroid-stimulating hormone receptor (TSHR). Iodine is captured by a hydrogen peroxide trap procuced by thyroid peroxidase and added to the 3' and 5' postitions of tyrosine. This can either be free tyrosine or a tyrosine residue in thyroglobuline. After the multiple iodination steps this produces T3 and T4. The production of the thyroid hormones thyroxine (T4),tri-iodothyronine (T3) and reverse T3 (rT3) is dependent on the organification of iodine into thyroglobulin (Tg), the major protein product of the thyroid (2). This involves thyroid peroxidase catalyzed iodination of tyrosine residues in Tg to form mono- and di-iodotyrosines and their subsequent crosslinking to form the iodothyronines T3 and T4. Iodine 131 is an important radioactive fallout product. It was released in the atmosphere after nuclear tests and after nuclear incidents like at Tchernobyl and Fukushima. Since the iodine is concentrated in the thyroid glant as a substrate for the process described here non-radioactive iodine 127 is given as competitor to people exposed. d2a bc3 f2a 30886364 PubMed The role of thyroglobulin in thyroid hormonogenesis. Nat Rev Endocrinol 2019 Citterio CE Targovnik HM Arvan P thyroid hormone signaling pathway PW:0000501 Pathway Ontology thyroid gland disease DOID:50 Disease thyroid hormone signaling pathway PW:0000501 Pathway Ontology 221813 PubMed Control of thyroglobulin synthesis and secretion N. Engl. J. Med. 301:239 1979 Van Herle, A.J . G. Vassart J.E . Dumont thyroid gland disease DOID:50 Disease 7871153 PubMed Thyroid cancer after exposure to external radiation: a pooled analysis of seven studies. Radiat Res 1995 Ron E Lubin JH Shore RE Mabuchi K Modan B Pottern LM Schneider AB Tucker MA Boice JD Jr