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The thyroid hormones, thyroxine (T4) and triiodothyronine (T3), are tyrosine-based hormones produced by the thyroid gland. They act on the body to increase the basal metabolic rate, affect protein synthesis and increase the body's sensitivity to catecholamines (such as adrenaline). An important component in the synthesis is iodine.
The major form of thyroid hormone in the blood is thyroxine (T4). This is converted to the active T3 within cells by deiodinases.
Most of the thyroid hormone circulating in the blood is bound to transport proteins :
- thyroid binding globulin (TBG)
- Thyroid binding prealbumin (TBPA) - this protein is also responsible for the transport of retinol, and so now has the preferred name of transthyretin (TTR)
- albumin
Only a very small fraction of the circulating hormone is free (unbound) - T4
0.03% and T3 0.3%. This free fraction is
biologically active, hence measuring concentrations of free thyroid hormones is
of great diagnostic value. These values are referred to as fT4 and fT3. Another critical diagnostic tool is the amount of thyroid-stimulating hormone that is present.
When thyroid hormone is bound, it is not active, the amount of free T3/T4 is what is important. For this reason, measuring total thyroxine in the blood can be misleading.
The thyroid hormones are essential to proper development and differentiation of all cells of human body. To various extent they regulate protein, fat and
carbohydrate metabolism. The most pronounced impact, however, is on
utilization of energetic compounds by human cells.
There are numerous physiological and pathological stimuli that influence the synthesis of thyroid hormones.
Thyrotoxicosis or hyperthyroidism is the clinical syndrome caused by an excess of circulating free thyroxine and free triiodothyronine, or both. It is a common disorder and affects approximately 2% of women and 0.2% of men.
Structure and production of the thyroid hormones
Thyroxine (3:5,3':5' tetraiodothyronine) is produced by follicular cells of the thyroid gland. It is produced as the precursor thyroglobulin (this is not the same as TBG), and this cleaved by enzymes to produce active T4.
Thyroxine is produced using the ring structures of tyrosine, to which iodine is attached. Thyroxine contains four iodine atoms, triiodothyronine is identical to T4, but it has one less iodine atom per molecule.
Iodide is actively absorbed from the bloodstream and concentrated in the thyroid follicles. (If there is a deficiency of dietary iodine, the thyroid enlarges in an attempt to trap more iodine, resulting in goitre) Via a reaction with the enzyme thyroperoxidase, iodine is covalently bound to tyrosine residues in the thyroglobulin molecules, forming monoiodotyrosine (MIT) and diiodotyrosine (DIT). By linking two moieties of DIT we have thyroxine and by combining one particle of MIT
and one particle of DIT we have triiodothyronine.
MIT + DIT = triiodothyronine (usually referred to as T3)
DIT + DIT = thyroxine (referred to as T4)
The iodinated thyroglobulin is digested by proteases, releasing the hormones - T4 and T3 are the biologically active agents central to regulation of metabolism. Thyroxine is supposedly a prohormone and a reservoir for the most active and main thyroid hormone T3, T4 being converted as required in the tissues by deiodinases.
Medical use of thyroid hormones
Both T3 and T4 are used to treat thyroid hormone deficiency (hypothyroidism). They are both absorbed well by the gut, so can be given orally.
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