Thyroxine (thyroid hormone) production (WP1981)

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.
last edited


Andra, Evelo, Mkutmon, Lribeiro, MaintBot, AlexanderPico, Egonw, and Eweitz

Cited In

Are you planning to include this pathway in your next publication? See How to Cite and add a link here to your paper once it's online.


Homo sapiens




Pathway Ontology: thyroid hormone signaling pathway thyroid hormone signaling pathway

Disease Ontology: thyroid gland disease thyroid gland disease


Label Type Compact Identifier
Triiodothyronine (T3) Metabolite chemspider:5707
TSH GeneProduct ncbigene:1081
127 Iodide Metabolite hmdb:HMDB0012238
TRH GeneProduct ncbigene:7200
TSHR GeneProduct ncbigene:7253
SLC5A5 GeneProduct ncbigene:6528
131 Iodide Metabolite pubchem.compound:167195
Thyruglobulin (Tg) GeneProduct ncbigene:7038
Thyroidperoxidase GeneProduct ncbigene:7173
L-Tyrosine Metabolite hmdb:HMDB0000158
Thyroxine (T4) Metabolite hmdb:HMDB0000248
131 Iodide Metabolite pubchem.compound:167195
127 Iodide Metabolite hmdb:HMDB0012238


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