Can be considered in 4 steps:
1. Iodide Trapping
- Iodine obtained in diet from dairy, grains and meat (150mg/day required)
- Reduced to the inorganic form iodide (I-)
- Actively taken up by thyroid follicular cells, stimulated by TSH:
- Transported against a concentration gradient by Na+/I- Symporter (NIS)
2. Iodide Oxidation & Organification
- Moves apically in the cell where is oxidised to iodine (I+)
- Requires the membrane bound enzyme thyroperoxidase
- I+ covalently binds to tyrosine residues on thyroglobulin in the colloid
- May be iodinated at one or two positions forming:
- Monoiodotyrosine (MIT)
- Diiodotyrosine (DIT)
3. Storage in Colloid with Thyroglobulin
- Tyrosine residues couple to form precursors of thryroid hormones:
- MIT & DIT couple to form T3
- DIT & DIT couple to from T4
- T3 & T4 remain attached to the thyroglobulin molecule for storage in colloid
4. Secretion of Thyroid Hormones
- When stimulated by TSH, thyroglobulin is internalised into the thyrocyte membrane via endocytosis
- Lysosomal endopeptidase cleaves the thyroglobulin releasing T3 and T4
- Thyroid hormones are released into the cytoplasm and diffuse into the bloodstream through the basement membrane