Thyroxine (thyroid hormone) production (WP3237)

Bos taurus

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.


Martina Summer-Kutmon , Egon Willighagen , and Eric Weitz


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Bos taurus



Disease Ontology

thyroid gland disease

Pathway Ontology

thyroid hormone signaling pathway


Label Type Compact Identifier Comment
Triiodothyronine (T3) Metabolite chemspider:5707
127 Iodide Metabolite hmdb:HMDB0012238
131 Iodide Metabolite pubchem.compound:167195
L-Tyrosine Metabolite hmdb:HMDB0000158
Thyroxine (T4) Metabolite hmdb:HMDB0000248
131 Iodide Metabolite pubchem.compound:167195
127 Iodide Metabolite hmdb:HMDB0012238
CGA GeneProduct ensembl:ENSBTAG00000016138 Homology Mapping from Homo sapiens to Bos taurus: Original ID = L:1081
TRH GeneProduct ensembl:ENSBTAG00000005306 Homology Mapping from Homo sapiens to Bos taurus: Original ID = L:7200
TSHR GeneProduct ensembl:ENSBTAG00000017489 Homology Mapping from Homo sapiens to Bos taurus: Original ID = L:7253
SLC5A5 GeneProduct ensembl:ENSBTAG00000015830 Homology Mapping from Homo sapiens to Bos taurus: Original ID = L:6528
TG GeneProduct ensembl:ENSBTAG00000007823 Homology Mapping from Homo sapiens to Bos taurus: Original ID = L:7038


  1. Control of thyroglobulin synthesis and secretion. (First of two parts). Van Herle AJ, Vassart G, Dumont JE. N Engl J Med. 1979 Aug 2;301(5):239–49. PubMed Europe PMC Scholia
  2. Thyroid cancer after exposure to external radiation: a pooled analysis of seven studies. Ron E, Lubin JH, Shore RE, Mabuchi K, Modan B, Pottern LM, et al. Radiat Res. 1995 Mar;141(3):259–77. PubMed Europe PMC Scholia