Synthesis of Thyroid Hormones: Thyroglobulin and its Iodination
Under TSH action, amino acids are transported into thyroid follicular cells and they are incorporated into the synthesis of a glycoprotein, thyroglobulin, which serves as a matrix in which thyroid hormones are formed. Thyroglobulin is synthesized on the rough endoplasmic reticulum (RER). Beginning carbohydrate moiety is added at the RER and the prohormone is "blebbed off" as vesicles that move toward the Golgi complex, where they fuse with Golgi vesicles and move into the complex. There, terminal carbohydrate is added to the molecule, condensation takes place, the prohormone is cleaved from the hormone, and thyroglobulin, mw 660,000, is packaged into colloid droplets. These droplets move toward the apex of the cell, toward the lumen of the follicle. The cell membrane adjacent to the lumen is covered with microvilli, which increase the surface for exocytosis or endocytosis.
TSH is also responsible for the active transport of I-, using Na+-K+ ATPase, into the follicular cell against a concentration gradient. Once in the cell the I- is rapidly oxidized by hydrogen peroxide, catalyzed by peroxidase, and converted to an "active intermediate," which is incorporated into the tyrosyl residues on the thyroglobulin molecule. The addition of "active iodide" takes place at the microvilli-apex of the cell just before the contents of the droplet are exocytosed into the lumen of the follicle (see top figure). Organification of I- on tyrosyl residues produces MIT and DIT on the thyroglobulin molecule. Active tyronines can also be formed on the thyroglobulin molecule in the lumen. When two DIT molecules are coupled, T4 is formed, while the coupling of one MIT and one DIT results in a T3 molecule; peroxidase is responsible for these reactions. (see bottom figure). Each thyroglobulin residue contains two MIT, four DIT, two T4 and one third T3, meaning only one in three thyroglobulins contain a T3. Thyroid hormones are stored as an integral part of the thyroglobulin matrix in the colloid of the follicular lumen.
Excessive iodine intake can block organification of iodine and therefore hormone synthesis. This inhibition usually lasts only several days and is known as the Wolff-Chaikoff effect.