Thyroid hormone synthesis includes the following steps, marked by numbers in the diagram above:
- I– trapping by the Na+/I– symporter into the thyroid follicular cells.
- Diffusion of I– to the apex of the cells.
- Transport of I– into the colloid, via pendrin.
- Oxidation of inorganic iodide to iodine (I0) by TPO and its incorporation into tyrosine residues within thyroglobulin in the colloid. DUOX2 and DUOXA2 are required for generation of hydrogen peroxide, a substrate for TPO.
- Combination of 2 DIT molecules by TPO to form T4, or of MIT with DIT to form T3.
- Uptake of thyroglobulin from the colloid into the follicular cell by endocytosis; fusion of the thyroglobulin with a lysosome; and proteolysis and release of T4, T3, DIT, and MIT.
- Release of T4 and T3 into the circulation.
- Deiodination of DIT and MIT by iodotyrosine deiodinase
(encoded by IYD, also known as iodotyrosine dehalogenase 1 [DEHAL1]), allowing recycling of I–.
T3 is also formed from monodeiodination of T4 in the thyroid and in peripheral tissues.
Illustration created by Mikael Häggström. Adapted under the Creative Commons CC0 1.0 Universal Public Domain Dedication.
