The functional unit of the thyroid gland is the follicle, composed of a single layer of epithelial cells surrounding a colloidal lumen in which thyroid hormone is stored as an integral part of its pre cursor protein thyroglobulin. The biosynthesis of thyroid hormone comprises the following steps, which are depicted schematically in Figure1:
1. Uptake of iodide through the basolateral membrane and export through the apical membrane.
2. Clustering of thyroglobulin, thyroid peroxidase (TPO) and the dual oxidase DUOX2 in a ‘thyroxisome’ at the luminal surface of the apical membrane.
3. Formation of H2O2 by DUOX2.
4. H2O2- dependent iodination of tyrosine residues in thyroglobulin by TPO.
5. H2O2- dependent coupling of iodotyrosine to iodothyronine residues in thyroglobulin by TPO.
6. Resorption of thyroglobulin from the lumen and hydrolysis in lysosomes.
7. Deiodination of iodotyrosines and reutilization of iodide.
8. Secretion of iodothyronines, predominantly T4, into the bloodstream.
Fig1. Schematic presentation of a thyroid follicular cell and important steps in the synthesis of thyroid hormone. DIT, 3,5- diiodotyrosine; MIT, monoiodotyrosine.
