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Most of the thyroid hormone circulating in the blood is bound to transport proteins. Only a very small fraction of the circulating hormone is free (unbound) and 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. For this reason, measuring total thyroxine in the blood can be misleading.
T1a and T0a are positively charged and do not cross the membrane; they are believed to function via the trace amine-associated receptor TAAR1 (TAR1, TA1), a G-protein-coupled receptor located in the cell membrane.
Another critical diagnostic tool is the amount of thyroid-stimulating hormone (TSH) that is present.
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. These hormones also regulate protein, fat, and carbohydrate metabolism, affecting how human cells use energetic compounds. They also stimulate vitamins metabolism. Numerous physiological and pathological stimuli influence thyroid hormone synthesis.
The thyronamines function via some unknown mechanism to inhibit neuronal activity; this plays an important role in the hibernation cycles of mammals and the moulting behaviour of birds. One effect of administering the thyronamines is a severe drop in body temperature.
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). They are both absorbed well by the gut, so can be given orally. 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.
Thyronamines have no medical usages yet, though their use has been proposed for controlled induction of hypothermia which causes the brain to enter a protective cycle, useful in preventing damage during ischemic shock.
Synthetic thyroxine was first successfully produced by Charles Robert Harington and George Barger in 1926.
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), which is cleaved by enzymes to produce active T4.
Thyroxine is produced by attaching iodine atoms to the ring structures of tyrosine molecules. Thyroxine(T4) contains four iodine atoms. Triiodothyronine(T3) is identical to T4, but it has one less iodine atom per molecule.
Iodide is actively absorbed from the bloodstream by a process called 'iodine trapping'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). Linking two moieties of DIT produces thyroxine. Combining one particle of MIT and one particle of DIT produces triiodothyronine.
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. T4 is converted as required in the tissues by deiodinases. Deficiency of deiodinase can mimic an iodine deficiency. T3 is more active than T4 and is the final form of the hormone, though it is present in less quantity than T4.
Iodine uptake against a concentration gradient is mediated by a sodium iodine symporter. Perchlorate and thiocyanate are drugs that can compete with iodine at this point.
Effects of thyroxine
|This article is licensed under the GNU Free Documentation License. It uses material from the Wikipedia article "Thyroid_hormone". A list of authors is available in Wikipedia.|