Role of thyroglobulin
The synthesis of thyroid hormones is inextricably linked to thyroglobulin (Tg). This is a glycoprotein containing 115 tyrosine amino acid residues in its structure.
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).
- Entry into the Golgi apparatus for further processing.
- Secretion by exocytosis into the extracellular space — the follicular colloid.
It is within the colloid that thyroglobulin is stored, and it is also where iodine is attached to its tyrosine residues.
Stages of iodothyronine biosynthesis
The hormone formation process 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 cell.
- Oxidation. At the apical membrane or directly within the colloid, iodine is oxidized with the participation of hydrogen peroxide ($H_2O_2$).
- Iodination. Oxidized iodine reacts with tyrosine residues within thyroglobulin. This reaction is catalyzed by the enzyme thyroperoxidase. As a result, monoiodotyronines (MIT) and diiodotyronines (DIT) are formed.
- 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 a secondary lysosome). Lysosomal enzymes trigger the proteolysis of thyroglobulin. During hydrolysis, free T3 and T4 hormones are released, which are then transported into the blood.
Forms of hormones and transport in the blood
In the body, thyroid hormones exist in several forms that differ in structure and function:
- T4 (thyroxine, 3,5,3',5'-tetraiodothyronine): is the main 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 (3,3',5'-triiodothyronine): a metabolite formed in the periphery by the cleavage 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 protein. This protein-hormone complex serves as a depot, a hormone reserve. The free (unbound) fraction is extremely small: for T4 it is only 0.03%, and for T3 — 0.3%. However, it is precisely this microscopic free fraction that provides all the biological activity of the hormones.
Briefly: answers to topical questions
Which hypothalamic and pituitary hormones regulate the synthesis of iodothyronines?
The synthesis of iodothyronines is regulated by hypothalamic thyrotropin-releasing hormone and pituitary thyroid-stimulating hormone. Regulation is carried out via a feedback mechanism in the hypothalamic-pituitary-thyroid axis.
- Thyrotropin-releasing hormone (TRH) — secreted by the hypothalamus and stimulates the release of thyroid-stimulating hormone by the pituitary gland.
- Thyroid-stimulating hormone (TSH) — produced by the adenohypophysis, stimulates the synthesis of thyroglobulin and the secretion of iodothyronines by the thyroid gland.
High concentrations of triiodothyronine and thyroxine in the blood suppress the secretion of thyrotropin-releasing hormone by the hypothalamus and TSH by the adenohypophysis via a negative feedback mechanism.
Class and exam questions
What is the difference between T3 and T4?
T4 (thyroxine) is the main form of the hormone secreted by the thyroid gland into the blood. T3 (triiodothyronine) is synthesized in smaller quantities, but it is the main biologically active form, as its affinity for cell receptors is 10 times higher than that of T4.
Where exactly does the iodination of thyroglobulin take place?
The process of attaching oxidized iodine to tyrosine residues within thyroglobulin occurs in the extracellular colloid of the thyroid follicles.
Which enzyme is responsible for iodination?
The reaction of interaction between oxidized iodine and tyrosine residues is catalyzed by the enzyme thyroperoxidase.
How is the synthesis of iodothyronines regulated?
The processes of synthesis and secretion of thyroid hormones are under the control of the hypothalamic-pituitary system.
What else to study on this topic
- Mechanism of action of the hypothalamic-pituitary system on the thyroid gland
- The process of T4 deiodination in peripheral tissues
- Structure and functions of thyroperoxidase
- The role of lysosomes in the secretion of thyroid hormones
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