Each epithelial cell of the thyroid follicle, or thyrocyte, is specialized to carry out all the steps required for the synthesis and secretion of T4 and T3. These are
1. Active transport of iodide into the thyroid gland follicular cells;
2. Oxidation of iodide and iodination of tyrosyl residues within the protein thyroglobulin;
3. Transfer and coupling of iodotyrosines within thyroglobulin to form T4 and T3;
4. Storage of thyroglobulin as the colloid in the lumen of the thyroid follicle;
5. Endocytosis of the colloid back into the thyroid epithelial cell;
6. Proteolysis of thyroglobulin with concomitant release of T4 and T3 as well as free iodotyrosines and iodothyronines;
7. Secretion of T4 and T3 into the blood;
8. Deiodination of iodotyrosines within the thy roid follicular cells for reutilization of the liberated iodine.
In order to carry out these functions, the thyroid follicular epithelial cell (thyrocyte) has a specialized architecture, reminiscent of other secretory cells, and cell-specific protein components including thyroglobulin (Tg), thyroid peroxidase (TPO), and the Na+/I− symporter (NIS). The two adjacent thyrocytes depicted in Figure 1 show the subcellular organelles of the thyrocyte and the locations of the proteins involved in thyroid hormone synthesis. Thyrocytes have polarity, with the basal end in contact with the capillary bed surrounding the follicle and the apical end in contact with the lumen of the follicle. The Na+/I− symporter is localized in the basal membrane of the cell and TPO is in the apical membrane. Much of the interior space of the basal and perinuclear portions of the thyrocyte is occupied by rough endoplasmic reticulum. A well developed Golgi apparatus is located apical to the nucleus as are the associated exocytotic vesicles for the secretion of thyroglobulin into the lumen of the follicle. In addition, the cell contains endocytotic vesicles and lysosomal structures that are responsible for the breakdown of thyroglobulin as discussed below. The apical surface of the thyrocyte is arranged as microvilli and some pseudopods.
Fig1. Thyroid epithelial cell structure and function. In the two thyrocytes shown, the organelles (left) and proteins (right) involved in thyroid hormone synthesis and secretion are depicted. The arrows in the thyrocyte on the left indicate the pathway of thyrogobulin (Tg) from its synthesis in the endoplasmic reticulum through the Golgi apparatus; secretion, accompanied by thyroid hormone synthesis (Tg with T4, T3, MIT, and DIT), into the lumen; re-uptake into the cell at the microvilli (M) or pseudopods (P) to form a colloid droplet (CD); breakdown in lysosomes (Ly) and release of thyroid hormone into the capillaries. At the basal membrane of the thyrocyte on the right, are shown NIS, the sodium/iodide transporter that is responsible for iodide uptake into the thyrocyte; TSHR=receptor for thyroid stimulating hormone; and MCT8=monocarboxylate transporter 8, which participates in secretion of T4 and T3 into the capillaries. At the apical membrane are TPO, thyroid peroxidase, which catalyzes the steps of thyroid hormone synthesis as Tg moves into the lumen and the dual oxidase, DUOX, which supplies peroxide (H2O2) for the reactions. Pendrin, a solute carrier protein, may participate in the movement of I− from the cell into the lumen of the thyrocyte. Within the cell, unused I− is removed from MIT (monoiodotyrosine) and DIT (diiodotyrosine) by DEHAL, iodotyrosine dehalogenase.
