Role of Thyroglobulin
The synthesis of thyroid hormones is inextricably linked to thyroglobulin (Tg). This is a glycoprotein whose structure contains 115 residues of the amino acid tyrosine.
The life cycle of thyroglobulin includes several stages:
- Synthesis of the protein chain on the ribosomes of the rough endoplasmic reticulum (ER) of the thyrocyte (in the basal part of the cell).
- Transport to the Golgi apparatus for further processing.
- Secretion via exocytosis into the extracellular space — the follicular colloid.
It is in the colloid that thyroglobulin is stored, and it is also where iodine is attached to its tyrosine residues.
Stages of Iodothyronine Biosynthesis
The process of hormone formation proceeds in a strictly sequential manner:
- Iodine transport. Iodide ions ($I^-$) are captured from the blood and transported across the basal membrane into the thyroid follicular cell.
- Oxidation. At the apical membrane or directly within the colloid, iodine is oxidized in the presence of hydrogen peroxide ($H_2O_2$).
- Iodination. Oxidized iodine reacts with tyrosine residues within the thyroglobulin molecule. This reaction is catalyzed by the enzyme thyroperoxidase. As a result, monoiodotyrosines (MIT) and diiodotyrosines (DIT) are formed.
- Coupling (Condensation). Iodinated molecules interact with each other:
- DIT + DIT form tetraiodothyronine, or thyroxine (T4).
- MIT + DIT form triiodothyronine (T3).
At this stage, the hormones are still bound to the thyroglobulin molecule in the colloid.
Secretion into the Blood
For active hormones to enter the bloodstream, the iodothyroglobulin complex must return to the thyrocyte. This occurs via endocytosis — the cell engulfs droplets of colloid.
Inside the cell, the resulting vesicles fuse with lysosomes (forming secondary lysosomes). Lysosomal enzymes trigger the proteolysis of thyroglobulin. Hydrolysis releases free T3 and T4 hormones, which are then transported into the blood.
Hormone Forms and Blood Transport
In the body, thyroid hormones exist in several forms that differ in structure and function:
- T4 (thyroxine, 3,5,3',5'-tetraiodothyronine): The primary secretory product of the thyroid gland.
- T3 (triiodothyronine, 3,5,3'-triiodothyronine): The main biologically active form of the hormone. Its affinity for target tissue receptors is 10 times higher than that of T4.
- Reverse T3 (rT3, 3,3',5'-triiodothyronine): A metabolite formed in peripheral tissues by the removal of iodine from the fifth carbon atom of the T4 molecule. It has virtually no biological activity.
Transport. Upon entering the blood, the vast majority of hormone molecules bind to thyroxine-binding globulin (TBG). This protein-hormone complex serves as a reservoir and depot for the hormones. The free (unbound) fraction is extremely small: for T4 it is only 0.03%, and for T3 it is 0.3%. However, it is this microscopic free fraction that provides all the biological activity of the hormones.