A collective term for iodine-containing amine hormones secreted from vertebrate thyroid glands. In humans and other mammals, the principle hormones are thyroxine (T4) and trilodothyronine (T3), which have important roles in fetal development and throughout life in the control of metabolism. Their synthesis and release is controlled by thyroid-stimulating hormone (TSH), a glycoprotein hormone produced in the front lobe of the pituitary gland of vertebrates, also known as thyrotrophin. In amphibian tadpoles, thyroid hormone is essential for metamorphosis.
The thyroid hormones, thyroxine (T4) and triiodothyronine (T3), are tyrosine-based hormones produced by the thyroid gland. The major form of thyroid hormone in the blood is thyroxine (T4). Thyroxine is converted to the active T3 (three to four times more potent than T4) within cells by deiodinases (5'-iodinase).
Circulation
Most of the thyroid hormone circulating in the blood is bound to transport proteins:
Thyroxine-binding globulin (TBG, 70%) Thyroxine-binding prealbumin (TBPA, 10-15%): this protein is also responsible for the transport of retinol, and so now has the preferred name of transthyretin (TTR) Albumin (15-20%).Only a very small fraction of the circulating hormone is free (unbound) - T4 0.03% and T3 0.3%. Free fraction of T3 is biologically active, hence measuring concentrations of free thyroid hormones is of great diagnostic value. When thyroid hormone is bound, it is not active, so the amount of free T3/T4 is what is important.
T3 and T4 cross the cell membrane and function via a well-studied set of receptors in the nucleus of the cell.
Function
The thyronines act on the body to increase the basal metabolic rate, affect protein synthesis and increase the body's sensitivity to catecholamines (such as adrenaline) by permissiveness. The thyroid hormones are essential to proper development and differentiation of all cells of the human body. Numerous physiological and pathological stimuli influence thyroid hormone synthesis.
Related diseases
Both excess and deficiency of thyroxine can cause disorders.
Medical use of thyroid hormones
Both T3 and T4 are used to treat thyroid hormone deficiency (hypothyroidism). Levothyroxine, the most commonly used synthetic thyroxine form, is a stereoisomer of physiological thyroxine, which is metabolised more slowly and hence usually only needs once-daily administration. Natural desiccated thyroid hormones, which are derived from pig thyroid glands, are a "natural" hypothyroid treatment containing 20% T3 and traces of T2, T1 and calcitonin.
Synthetic thyroxine was first successfully produced by Charles Robert Harrington and George Barger in 1926.
Structure and production of the thyroid hormones
Thyroxine (3,5,3',5'-tetraiodothyronine) is produced by follicular cells of the thyroid gland.
Thyroxine is produced by attaching iodine atoms to the ring structures of tyrosine molecules.
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).
MIT + DIT = triiodothyronine (usually referred to as T3) DIT + DIT = thyroxine (referred to as T4)Proteases digest iodinated thyroglobulin, releasing the hormones T4 and T3, the biologically active agents central to metabolic regulation. Thyroxine is supposedly a prohormone and a reservoir for the most active and main thyroid hormone T3. T3 is more active than T4 and is the final form of the hormone, though it is present in less quantity than T4.
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