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
Thyroid hormone formation, synthesis and release