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07-SEPTEMBER-2008 03:17:44 - Thyroid hormone thyroxine T4 thyroxine T4 triiodothyronine T3 triiodothyronine T3 Thyroxine, T4 Thyroxine, T4 Triiodothyronine, T3 Triiodothyronine, T3 The thyroid hormones, thyroxine T4 and triiodothyronine T3, are tyrosine-based hormones produced by the thyroid gland. An important component in the synthesis is iodine. The major form of thyroid hormone in the blood is thyroxine T4. The ratio of T4 to T3 released in the blood is roughly 20 to 1. Thyroxine is converted to the active T3 three to four times more potent than T4 within cells by deiodinases 5'-iodinase. These are further processed by decarboxylation and deiodination to produce iodothyronamine T1a and thyronamine T0a. Contents 1 Circulation 2 Function 3 Related diseases 4 Medical use of thyroid hormones 5 Production of the thyroid hormones 6 Anti-thyroid drugs 7 Effects of thyroxine 8 References 9 See also 10 External links Circulation 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. Type Percent bound to thyroxine-binding globulin TBG 70% bound to transthyretin or thyroxine-binding prealbumin TTR or TBPA 10-15% albumin 15-20% unbound T4 fT4 0.03% unbound T3 fT3 0.3% T3 and T4 cross the cell membrane, probably via amino acid importins, and function via a well-studied set of nuclear receptors in the nucleus of the cell, the thyroid hormone receptors. 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 measurement of the amount of thyroid-stimulating hormone TSH that is present. 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. These hormones also regulate protein, fat, and carbohydrate metabolism, affecting how human cells use energetic compounds. They also stimulate vitamin metabolism. Numerous physiological and pathological stimuli influence thyroid hormone synthesis. Thyroid hormone leads to heat generation in humans. However, 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. Related diseases Both excess and deficiency of thyroxine can cause disorders. Thyrotoxicosis or hyperthyroidism an example is Graves Disease is the clinical syndrome caused by an excess of circulating free thyroxine, free triiodothyronine, or both. It is a common disorder that affects approximately 2% of women and 0.2% of men. Hypothyroidism an example is Hashimoto's thyroiditis is the case where there is a deficiency of thyroxine, triiodiothyronine, or both. Clinical depression can sometimes be caused by hypothyroidism1. Some research2 has shown that T3 is found in the junctions of synapses, and regulates the amounts and activity of serotonin, norepinephrine, and Gamma-aminobutyric acid GABA in the brain. 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, also under the commercial name Armour Thyroid, is derived from pig thyroid glands, it is a natural hypothyroid treatment containing 20% T3 and traces of T2, T1 and calcitonin. Also available are synthetic combinations of T3/T4 in different ratios such as Thyrolar and pure-T3 medications Cytomel. 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'-tetra-iodothyronine 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. DIT + MIT → r-T3 biologically inactive 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. 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. Anti-thyroid drugs 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 Increases cardiac output Increases heart rate Increases ventilation rate Increases basal metabolic rate Potentiates the effects of catecholamines i.e increases sympathetic activity Potentiates brain development Thickens endometrium in females References ^ Kirkegaard C, Faber J 1998. The role of thyroid hormones in depression. Eur J Endocrinol 138 1: 1-9. doi:10.1530/eje.0.1380001. PMID 9461307. ^ Dratman M, Gordon J 1996. Thyroid hormones as neurotransmitters. Thyroid 6 6: 639-47. PMID 9001201. See also Hormone Thyroid gland Thyroid-stimulating hormone Thyronamines, metabolites of the thyroid hormones that act at the trace amine-associated receptor TAAR1 TAR1 Goitre Graves-Basedow disease External links Collection of medical articles on Thyroid disease including the hormones Find TH response elements in DNA sequences. Collection of references to articles comparing different treatment methods of hypothyroidism v d e Endocrine system: hormones/endocrine glands Peptide hormones, Steroid hormones Hypothalamic-pituitary Hypothalamus: TRH, CRH , GnRH, GHRH, somatostatin, dopamine - Posterior pituitary: vasopressin, oxytocin - Anterior pituitary: α FSH, LH, TSH, GH, prolactin, POMC ACTH, MSH, endorphins, lipotropin Adrenal axis Adrenal medulla: epinephrine, norepinephrine - Adrenal cortex: aldosterone, cortisol, DHEA Thyroid axis Thyroid: thyroid hormone T3 and T4 - calcitonin - Parathyroid: PTH Gonadal axis Testis: testosterone, AMH, inhibin - Ovary: estradiol, progesterone, inhibin/activin, relaxin pregnancy Other end. glands Pancreas: glucagon, insulin, somatostatin - Pineal gland: melatonin Non-end. glands Placenta: hCG, HPL, estrogen, progesterone - Kidney: renin, EPO, calcitriol, prostaglandin - Heart atrium: ANP - Stomach: gastrin, ghrelin - Duodenum: CCK, GIP, secretin, motilin, VIP - Ileum: enteroglucagon - Adipose tissue: leptin, adiponectin, resistin - Thymus: Thymosin - Thymopoietin - Thymulin - Skeleton: Osteocalcin - Liver/other: Insulin-like growth factor IGF-1, IGF-2 Target-derived NGF, BDNF, NT-3 v d e Thyroid therapy H03 Thyroid hormones Levothyroxine sodium - Liothyronine sodium - Tiratricol - Thyroid gland preparations Antithyroid preparations Thiouracils Methylthiouracil, Propylthiouracil, Benzylthiouracil Sulfur-containing imidazole derivatives Carbimazole, Thiamazole Perchlorates Potassium perchlorate Other Diiodotyrosine, Dibromotyrosine Retrieved from http://en..org/wiki/Thyroid_hormone Categories: Iodinated tyrosine derivatives | Thyroid hormones | HPT axis Views Article Discussion this page History Personal tools Log in / create account Navigation Main page Contents Featured content Current events Random article Search Go Search Interaction Community portal Recent changes Contact Donate to Help Toolbox What links here Related changes Upload file Special pages Printable version Permanent link Cite this page Languages Türkçe БългарÑ?ки ÄŒesky Deutsch Español Français עברית Nederlands 日本語 РуÑ?Ñ?кий This page was last modified on 17 August 2008, at 05:29
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