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{{BioPsy}}
 
{{BioPsy}}
  +
[[Image:Thyroxine-2D-skeletal.png|thumb|[[thyroxine]] (T<sub>4</sub>)]]
  +
[[Image:Triiodothyronine.svg|thumb|[[triiodothyronine]] (T<sub>3</sub>)]]
  +
[[Image:T4-3D-vdW.png|thumb|right|200px|Thyroxine, T<sub>4</sub>]]
  +
[[Image:T3-3D-vdW.png|thumb|right|200px| Triiodothyronine, T<sub>3</sub>]]
   
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>). This is converted to the active T<sub>3</sub> within [[cell (biology)|cell]]s by deiodinases. These are further processed by decarboxylation and deiodination to produce '''iodothyronamine''' ('''T<sub>1</sub>a''') and '''[[thyronamine]]''' ('''T<sub>0</sub>a''').
+
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''').
   
 
==Circulation==
 
==Circulation==
Most of the thyroid hormone circulating in the [[blood]] is bound to transport [[protein]]s :
 
* [[Thyroxine-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) - T<sub>4</sub>
 
0.03% and T<sub>3</sub> 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 fT<sub>4</sub> and fT<sub>3</sub>. Another critical diagnostic tool is the amount of [[thyroid-stimulating hormone]] that is present. 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.
 
   
==Function==
+
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.
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]]).The thyroid hormones are essential to proper development and differentiation of all cells of the human body. To various extents, they regulate protein, fat and carbohydrate [[metabolism]]. But they have their most pronounced effects on how human [[cell (biology)|cell]]s use energetic compounds. Numerous physiological and pathological stimuli influence thyroid hormone synthesis.
 
   
The thyronamines function via some unknown mechanism to inhbit [[neuron]]al activity; this plays an important role in the [[hibernation]] cycles of [[mammals]]. One effect of administering the thyronamines is a severe drop in [[body temperature]].
+
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.
   
==Related diseases==
+
{| class="wikitable"
Both excess and deficiency of thyroxine can cause disorders.
+
| '''Type''' || '''Percent'''
* Thyrotoxicosis or [[hyperthyroidism]] 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]] is the case where there is a lack of thyroxine.
+
| bound to [[thyroxine-binding globulin]] (TBG)|| 70%
  +
|-
  +
| bound to [[transthyretin]] or "thyroxine-binding prealbumin" (TTR or TBPA) || 10-15%
  +
|-
  +
| [[serum albumin|paraalbumin]] || 15-20%
  +
|-
  +
| unbound T<sub>4</sub> (fT<sub>4</sub>) || 0.03%
  +
|-
  +
| unbound T<sub>3</sub> (fT<sub>3</sub>) || 0.3%
  +
|}
   
==Medical use of thyroid hormones==
+
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.
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 form, is a [[stereoisomer]] of physiological thyroxine, which is metabolised more slowly and hence usually only needs once-daily administration.
 
   
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]].
+
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]].
   
==Structure and production of the thyroid hormones==
+
Another critical diagnostic tool is measurement of the amount of [[thyroid-stimulating hormone]] (TSH) that is present.
[[Image:Thyroxine.png|right|Chemical structure of thyroxine]]
 
   
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>.
+
== Function ==
   
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.
+
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. They also stimulate vitamin metabolism. Numerous physiological and pathological stimuli influence thyroid hormone synthesis.
   
[[Iodine|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). Linking two moieties of DIT produces [[thyroxine]]. Combining one particle of MIT
+
Thyroid hormone leads to heat generation in humans. However, 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]].
and one particle of DIT produces [[triiodothyronine]].
 
   
* MIT + DIT = [[triiodothyronine]] (usually referred to as T<sub>3</sub>)
+
== Related diseases ==
* DIT + DIT = [[thyroxine]] (referred to as T<sub>4</sub>)
 
   
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 as 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>.
+
Both excess and deficiency of thyroxine can cause disorders.
   
==Effects of thyroxine==
+
* 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.
* increased cardiac output
+
* [[Hypothyroidism]] (an example is [[Hashimoto's thyroiditis]]) is the case where there is a deficiency of thyroxine, triiodiothyronine, or both.
* increased heart rate
+
* [[Clinical depression]] can sometimes be caused by hypothyroidism<ref name="depression">{{cite journal
* increased ventilation rate
+
| author = Kirkegaard C, Faber J
* increased basal metabolic rate
+
| title = The role of thyroid hormones in depression
  +
| journal = Eur J Endocrinol
  +
| volume = 138
  +
| issue = 1
  +
| pages = 1–9
  +
| year = 1998
  +
| pmid = 9461307
  +
| doi = 10.1530/eje.0.1380001
  +
}}</ref>. Some research<ref name="neuro">{{cite journal
  +
| author = Dratman M, Gordon J
  +
| title = Thyroid hormones as neurotransmitters
  +
| journal = Thyroid
  +
| volume = 6
  +
| issue = 6
  +
| pages = 639–47
  +
| year = 1996
  +
| pmid = 9001201
  +
}}</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]].
   
==External links==
+
== Medical use of thyroid hormones ==
*[http://www.suite101.com/article.cfm/graves_disease/68414 Discussion of thyroxine treatment.]
+
*[http://www.thyroidmanager.org/ Collection of medical articles on Thyroid disease including the hormones]
+
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]], also under the commercial name [[Armour Thyroid]], is derived from pig thyroid glands, it is a "natural" hypothyroid treatment containing 20% T<sub>3</sub> and traces of T<sub>2</sub>, T<sub>1</sub> 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 [[ischemia|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 [[Thyroxine-binding globulin|TBG]]), which is cleaved by enzymes to produce active T<sub>4</sub>.
  +
  +
Thyroxine is produced by attaching iodine atoms to the ring structures of [[tyrosine]] molecules. Thyroxine (T<sub>4</sub>) contains four iodine atoms. Triiodothyronine (T<sub>3</sub>) is identical to T<sub>4</sub>, 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 [[Iodine deficiency|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-T<sub>3</sub> (biologically inactive)
  +
* MIT + DIT → triiodothyronine (usually referred to as T<sub>3</sub>)
  +
* DIT + DIT → thyroxine (referred to as T<sub>4</sub>)
  +
  +
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>.
  +
  +
== 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 ==
  +
<references/>
  +
  +
== See also ==
  +
* [[Hormone]]
  +
* [[Thyroid]] gland
  +
* [[Thyroid-stimulating hormone]]
  +
* [[Thyronamine]]s, metabolites of the thyroid hormones that act at the trace amine-associated receptor TAAR1 (TAR1)
  +
* [[Goitre]]
  +
* [[Graves-Basedow disease]]
  +
  +
== External links ==
  +
* [http://www.thyroidmanager.org/ Collection of medical articles on Thyroid disease including the hormones]
  +
* [http://www.tre-search.com/ Find TH response elements in DNA sequences.]
  +
* [http://www.stopthethyroidmadness.com/references/ Collection of references to articles comparing different treatment methods of hypothyroidism]
  +
  +
{{Hormones}}
  +
{{Thyroid therapy}}
   
{{Template:Hormones}}
 
   
[[Category:Hormones]]
 
[[Category:HPT axis]]
 
[[Category:Iodinated tyrosine derivatives]]
 
 
[[Category:Thyroid hormones]]
 
[[Category:Thyroid hormones]]
  +
[[Category:HPT axis]]
   
   
 
<!--
 
<!--
  +
 
[[bg:Трийодтиронин]]
 
[[bg:Трийодтиронин]]
[[cs:Thyroxin]]
+
[[cs:Hormony štítné žlázy]]
[[de:Triiodthyronin]]
+
[[de:Schilddrüsenhormon]]
[[es:Tiroxina]]
+
[[es:Hormona tiroidea]]
[[fi:Tyroksiini]]
+
[[fr:Hormone thyroïdienne]]
[[fr:Thyroxine]]
 
 
[[he:תריודוטירונין]]
 
[[he:תריודוטירונין]]
  +
[[nl:Schildklierhormonen]]
 
[[ja:甲状腺ホルモン]]
 
[[ja:甲状腺ホルモン]]
[[nl:Trijodothyronine]]
 
[[pl:Tyroksyna]]
 
[[pt:Tiroxina]]
 
 
[[ru:Тиреоидные гормоны]]
 
[[ru:Тиреоидные гормоны]]
 
[[tr:Tiroid hormonları]]
 
[[zh:甲状腺素]]
 
 
-->
 
-->
 
{{enWP|Thyroid hormone}}
 
{{enWP|Thyroid hormone}}

Latest revision as of 23:56, January 9, 2009

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File:Thyroxine-2D-skeletal.png
File:Triiodothyronine.svg
File:T4-3D-vdW.png
File:T3-3D-vdW.png

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).

CirculationEdit

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%
paraalbumin 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 Edit

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 Edit

Both excess and deficiency of thyroxine can cause disorders.

Medical use of thyroid hormones Edit

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 Edit

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.

  • 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 Edit

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 Edit

  • 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 Edit

  1. Kirkegaard C, Faber J (1998). The role of thyroid hormones in depression. Eur J Endocrinol 138 (1): 1–9.
  2. Dratman M, Gordon J (1996). Thyroid hormones as neurotransmitters. Thyroid 6 (6): 639–47.

See also Edit

External links Edit


|}

Target-derived NGF, BDNF, NT-3

|}

Template:Thyroid therapy


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