Thyroxine (thyroid hormone) production (WP1981)

Homo sapiens

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.


Andra Waagmeester , Chris Evelo , Martina Summer-Kutmon , Lucia Ribeiro , Alex Pico , Egon Willighagen , Eric Weitz , and Celine Malyar


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Homo sapiens




Pathway Ontology

thyroid hormone signaling pathway thyroid hormone signaling pathway

Disease Ontology

thyroid gland disease thyroid gland disease


Label Type Compact URI Comment
ATP Metabolite hmdb:HMDB0001532
H202 Metabolite chebi:16240
cAMP Metabolite hmdb:HMDB0000058
PtdIns(4,5)P2 Metabolite chebi:83416
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
Ins(1,4,5)P3 Metabolite chebi:138527
DAG Metabolite chebi:18035
Ca2+ Metabolite chebi:29108
131 Iodide Metabolite pubchem.compound:167195
127 Iodide Metabolite hmdb:HMDB0012238
TSH GeneProduct ncbigene:1081
TRH GeneProduct ncbigene:7200
Thyruglobulin (Tg) GeneProduct ncbigene:7038
Thyroidperoxidase GeneProduct ncbigene:7173
TSHR GeneProduct ncbigene:7253
ADCY1 GeneProduct ensembl:ENSG00000243989
PRKAA1 GeneProduct ensembl:ENSG00000132356
PRKAAK2 GeneProduct ensembl:ENSG00000162409
CREB1 GeneProduct uniprot:P16220
CREB1 GeneProduct uniprot:P16220
RAP1A GeneProduct uniprot:P62834
RAP1B GeneProduct uniprot:P61224
MAPK21 GeneProduct ensembl:ENSG00000169032
MAP2K2 GeneProduct ensembl:ENSG00000126934
ERK1 GeneProduct ncbigene:5595
ERK2 GeneProduct ncbigene:5594
ELK1 GeneProduct ncbigene:2002
PLC GeneProduct uniprot:PP51178
PRKCA GeneProduct ensembl:ENSG00000154229
RAF1 GeneProduct uniprot:P04049
NF-KB GeneProduct uniprot:P19838
SLC5A5 GeneProduct ncbigene:6528
SLC26A6 GeneProduct ensembl:ENSG00000225697
ANO1 GeneProduct ensembl:ENSG00000131620
CLC5 GeneProduct ensembl:ENSG00000171365
DUOX1 GeneProduct ensembl:ENSG00000137857
DUOX2 GeneProduct ensembl:ENSG00000140279


  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
  3. The role of thyroglobulin in thyroid hormonogenesis. Citterio CE, Targovnik HM, Arvan P. Nat Rev Endocrinol. 2019 Jun;15(6):323–38. PubMed Europe PMC Scholia