https://www.wikidoc.org/index.php?title=Thyroid_hormone&feed=atom&action=historyThyroid hormone - Revision history2024-03-29T08:38:05ZRevision history for this page on the wikiMediaWiki 1.40.0https://www.wikidoc.org/index.php?title=Thyroid_hormone&diff=690231&oldid=prevWikiBot: Robot: Automated text replacement (-{{SIB}} +, -{{EH}} +, -{{EJ}} +, -{{Editor Help}} +, -{{Editor Join}} +)2012-08-20T16:55:23Z<p>Robot: Automated text replacement (-{{SIB}} +, -{{EH}} +, -{{EJ}} +, -{{Editor Help}} +, -{{Editor Join}} +)</p>
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<p><b>New page</b></p><div>[[Image:Triiodothyronine_svg.png|thumb|[[triiodothyronine]] (T3)]]<br />
[[Image:Thyroxine-2D-skeletal.png|thumb|[[thyroxine]] (T4)]]<br />
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==Overview==<br />
The '''thyroid hormones''', [[thyroxine]] ('''T<sub>4</sub>''') and [[triiodothyronine]] ('''T<sub>3</sub>'''), are [[tyrosine]]-based [[hormone]]s produced by the [[thyroid gland]]. An important component in the synthesis is [[iodine]]. The major form of thyroid hormone in the blood is thyroxine (T<sub>4</sub>). The ratio of T<sub>4</sub> to T<sub>3</sub> released in the blood is roughly 20 to 1. Thyroxine is converted to the active T<sub>3</sub> (three to four times more potent than T<sub>4</sub>) within [[cell (biology)|cell]]s by [[deiodinase]]s (5'-iodinase). These are further processed by [[decarboxylation]] and deiodination to produce [[iodothyronamine]] ('''T<sub>1</sub>a''') and [[thyronamine]] ('''T<sub>0</sub>a''').<br />
<br />
==Circulation==<br />
<br />
Most of the thyroid hormone circulating in the [[blood]] is bound to transport [[protein]]s. 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. <br />
<br />
When thyroid hormone is bound, it is not active, so the amount of free T<sub>3</sub>/T<sub>4</sub> is what is important. For this reason, measuring total thyroxine in the blood can be misleading.<br />
<br />
{| class="wikitable"<br />
| '''Type''' || '''Percent''' <br />
|- <br />
| bound to [[thyroxine-binding globulin]] (TBG)|| 70% <br />
|- <br />
| bound to [[transthyretin]] or "thyroxine-binding prealbumin" (TTR or TBPA) || 10-15% <br />
|- <br />
| [[serum albumin|albumin]] || 15-20% <br />
|- <br />
| unbound T<sub>4</sub> (fT<sub>4</sub>) || 0.03%<br />
|- <br />
| unbound T<sub>3</sub> (fT<sub>3</sub>) || 0.3% <br />
|}<br />
<br />
T<sub>3</sub> and T<sub>4</sub> cross the [[cell membrane]], probably via amino acid [[importins]], and function via a well-studied set of [[Nuclear receptor|nuclear]] [[receptor (biochemistry)|receptors]] in the [[cell nucleus|nucleus]] of the cell, the [[Thyroid hormone receptor|thyroid hormone receptor]]s. <br />
<br />
T<sub>1</sub>a and T<sub>0</sub>a are positively charged and do not cross the membrane; they are believed to function via the [[trace amine-associated receptor]] {{Gene|TAAR1}} (TAR1, TA1), a [[G-protein-coupled receptor]] located in the [[cell membrane]].<br />
<br />
Another critical diagnostic tool is the amount of [[thyroid-stimulating hormone]] (TSH) that is present.<br />
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== Function ==<br />
<br />
The thyronines act on the body to increase the [[basal metabolic rate]], affect [[protein synthesis]] and increase the body's sensitivity to [[catecholamine]]s (such as [[adrenaline]]) by [[permissiveness (biology)|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 [[cell (biology)|cell]]s use energetic compounds. Numerous physiological and pathological stimuli influence thyroid hormone synthesis.<br />
<br />
The thyronamines function via some unknown mechanism to inhibit [[neuron]]al 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]].<br />
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== Related diseases ==<br />
<br />
Both excess and deficiency of thyroxine can cause disorders.<br />
<br />
* Thyrotoxicosis or [[hyperthyroidism]] (more specifically [[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.<br />
* [[Hypothyroidism]] (an example is [[Hashimoto's thyroiditis]]) is the case where there is a deficiency of thyroxine, triiodiothyronine, or both.<br />
* [[Clinical depression]] can sometimes be caused by hypothyroidism<ref name="depression">{{cite journal<br />
| author = Kirkegaard C, Faber J<br />
| title = The role of thyroid hormones in depression.<br />
| journal = Eur J Endocrinol<br />
| volume = 138<br />
| issue = 1<br />
| pages = 1-9<br />
| year = 1998<br />
| id = PMID 9461307<br />
}}</ref>. Some research<ref name="neuro">{{cite journal<br />
| author = Dratman M, Gordon J<br />
| title = Thyroid hormones as neurotransmitters.<br />
| journal = Thyroid<br />
| volume = 6<br />
| issue = 6<br />
| pages = 639-47<br />
| year = 1996<br />
| id = PMID 9001201<br />
}}</ref> has shown that T<sub>3</sub> is found in the junctions of [[Chemical synapse|synapse]]s, and regulates the amounts and activity of [[serotonin]], [[norepinephrine]], and [[Gamma-aminobutyric acid]] (GABA) in the [[brain]].<br />
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== Medical use of thyroid hormones ==<br />
<br />
Both T<sub>3</sub> and T<sub>4</sub> 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.<br />
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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 [[ischemia|ischemic shock]].<br />
<br />
Synthetic thyroxine was first successfully produced by [[Charles Robert Harington]] and [[George Barger]] in 1926.<br />
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== Structure and production of the thyroid hormones ==<br />
[[Image:L-tyrosine-skeletal.png|thumb|left|200px|[[Tyrosine]]]]<br />
[[Image:T4-3D-vdW.png|thumb|left|200px|Thyroxine, T<sub>4</sub>]]<br />
[[Image:T3-3D-vdW.png|thumb|left|200px| Triiodothyronine, T<sub>3</sub>]]<br />
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 T<sub>4</sub>.<br />
<br />
Thyroxine is produced by attaching iodine atoms to the ring structures of tyrosine molecules. Thyroxine contains four iodine atoms. Triiodothyronine is identical to T<sub>4</sub>, but it has one less iodine atom per molecule.<br />
<br />
[[Iodine|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<br />
and one particle of DIT produces triiodothyronine.<br />
<br />
* MIT + DIT → triiodothyronine (usually referred to as T<sub>3</sub>)<br />
* DIT + DIT → thyroxine (referred to as T<sub>4</sub>)<br />
<br />
Proteases digest iodinated thyroglobulin, releasing the hormones T<sub>4</sub> and T<sub>3</sub>, the biologically active agents central to metabolic regulation. Thyroxine is supposedly a [[prohormone]] and a reservoir for the most active and main thyroid hormone T<sub>3</sub>. T<sub>4</sub> is converted as required in the tissues by [[deiodinase]]s. Deficiency of deiodinase can mimic an iodine deficiency. T<sub>3</sub> is more active than T<sub>4</sub> and is the final form of the hormone, though it is present in less quantity than T<sub>4</sub>.<br />
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== Anti-thyroid drugs ==<br />
<br />
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.<br />
<br />
== Effects of thyroxine ==<br />
* Increases [[cardiac output]]<br />
* Increases heart rate<br />
* Increases ventilation rate<br />
* Increases [[basal metabolic rate]]<br />
* Potentiates brain development<br />
* Thickens [[endometrium]] in females<br />
<br />
== References ==<br />
<references/><br />
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== See also ==<br />
* [[Hormone]]<br />
* [[Thyroid]] gland<br />
* [[Thyroid-stimulating hormone]]<br />
* [[Thyronamine]]s, metabolites of the thyroid hormones that act at the trace amine-associated receptor TAAR1 (TAR1)<br />
* [[Goitre]]<br />
* [[Graves-Basedow disease]]<br />
<br />
== External links ==<br />
* {{McGrawHillAnimation|biochemistry|Thyroid%20Hormone}}<br />
* [http://www.thyroidmanager.org/ Collection of medical articles on Thyroid disease including <br />
the hormones]<br />
* [http://www.tre-search.com/ Find TH response elements in DNA sequences.]<br />
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{{Hormones}}<br />
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[[Category:Iodinated tyrosine derivatives]]<br />
[[Category:Thyroid hormones]]<br />
[[Category:HPT axis]]<br />
[[Category:Endocrinology]]<br />
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