Triiodothyronine

Source: Wikipedia, the free encyclopedia.
This article is about triiodothyronine as a hormone. For its use as a pharmaceutical drug, see Liothyronine.
Triiodothyronine
Liothyronine2DCSD.svg
Triiodothyronine-T3-from-xtal-3D-bs-17.png
Triiodothyronine-T3-from-xtal-3D-sf.png
Names
IUPAC name
(2S)-2-amino-3-[4-(4-hydroxy-3-iodophenoxy)-3,5-diiodophenyl]propanoic acid
Other names
triiodothyronine
T3
3,3′,5-triiodo-L-thyronine
Identifiers
3D model (
JSmol
)
2710227
ChEBI
ChEMBL
ChemSpider
DrugBank
ECHA InfoCard
 100.027.272 Edit this at Wikidata
EC Number
  • 229-999-3
IUPHAR/BPS
KEGG
UNII
  • InChI=1S/C15H12I3NO4/c16-9-6-8(1-2-13(9)20)23-14-10(17)3-7(4-11(14)18)5-12(19)15(21)22/h1-4,6,12,20H,5,19H2,(H,21,22)/t12-/m0/s1 checkY
    Key: AUYYCJSJGJYCDS-LBPRGKRZSA-N checkY
  • InChI=1/C15H12I3NO4/c16-9-6-8(1-2-13(9)20)23-14-10(17)3-7(4-11(14)18)5-12(19)15(21)22/h1-4,6,12,20H,5,19H2,(H,21,22)/t12-/m0/s1
    Key: AUYYCJSJGJYCDS-LBPRGKRZBY
  • OC(=O)[C@@H](N)Cc1cc(I)c(c(I)c1)Oc2ccc(O)c(I)c2
Properties
C15H12I3NO4
Molar mass 650.977 g·mol−1
Hazards
GHS labelling:
GHS07: Exclamation mark
Warning
H315, H319, H335
P261, P264, P271, P280, P302+P352, P304+P340, P305+P351+P338, P312, P321, P332+P313, P337+P313, P362, P403+P233, P405, P501
NFPA 704 (fire diamond)
1
1
0
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
checkY verify (what is checkY☒N ?)

Triiodothyronine, also known as T3, is a

body temperature, and heart rate.[1]

Production of T3 and its

bloodstream
.

T3 is the true hormone. Its effects on target tissues are roughly four times more potent than those of T4.[2] Of the thyroid hormone that is produced, just about 20% is T3, whereas 80% is produced as T4. Roughly 85% of the circulating T3 is later formed in the liver and anterior pituitary by removal of the iodine atom from the carbon atom number five of the outer ring of T4. In any case, the concentration of T3 in the human blood plasma is about one-fortieth that of T4. The half-life of T3 is about 2.5 days.[3] The half-life of T4 is about 6.5 days.[4]

Production

Synthesis from T4

Thyroid hormone synthesis, with the end-product of triiodothyroninе seen at bottom right[5]
See also: Iodothyronine deiodinase § Types

T3 is the more metabolically active hormone produced from T4. T4 is deiodinated by three deiodinase enzymes to produce the more-active triiodothyronine:

  1. Type I present in liver, kidney, thyroid, and (to a lesser extent) pituitary; it accounts for 80% of the deiodination of T4.
  2. Type II present in CNS, pituitary, brown adipose tissue, and heart vessel, which is predominantly intracellular. In the pituitary, it mediates negative feedback on thyroid-stimulating hormone.
  3. Type III present in placenta, CNS, and hemangioma. This deiodinase converts T4 into
    reverse T3
    , which, unlike T3, is inactive.

T4 is synthesised in the thyroid follicular cells as follows.

  1. The
    sodium-iodide symporter
    transports two sodium ions across the basement membrane of the follicular cells along with an iodine ion. This is a secondary active transporter that utilises the concentration gradient of Na+ to move I− against its concentration gradient.
  2. I− is moved across the apical membrane into the colloid of the follicle.
  3. Thyroperoxidase
    oxidises I− to form the I radical.
  4. The thyroperoxidase iodinates the tyrosyl residues of the thyroglobulin within the colloid. The thyroglobulin was synthesised in the ER of the follicular cell and secreted into the colloid.
  5. Thyroid-stimulating hormone (TSH) released from the anterior pituitary gland binds the TSH receptor (a Gs protein-coupled receptor) on the basolateral membrane of the cell and stimulates the endocytosis of the colloid.
  6. The endocytosed vesicles fuse with the lysosomes of the follicular cell. The lysosomal enzymes cleave the T4 from the iodinated thyroglobulin.
  7. These vesicles are then exocytosed, releasing the thyroid hormones.
Synthesis of T3 from T4 via deiodination. Synthesis of reverse T3 and T2
is also shown.

Direct synthesis

The thyroid gland also produces small amounts of T3 directly. In the

monoiodotyrosine (MIT) and diiodotyrosine (DIT). One MIT and one DIT are enzymatically coupled to form T3. The enzyme is thyroid peroxidase
.

The small amount of T3 could be important because different tissues have different sensitivities to T4 due to differences in deiodinase ubiquitination in different tissues.[6] This once again raises the question if T3 should be included in thyroid hormone replacement therapy (THRT).

Mechanism of action

T3 and T4 bind to

thyroxine binding prealbumins, and albumins
) for transport in the blood. The thyroid receptors bind to response elements in gene promoters, thus enabling them to activate or inhibit transcription. The sensitivity of a tissue to T3 is modulated through the thyroid receptors.

Transportation

T4[9]

T3 and T4 are carried in the blood, bound to plasma proteins. This has the effect of increasing the half-life of the hormone and decreasing the rate at which it is taken up by peripheral tissues. There are three main proteins that the two hormones are bound to. Thyroxine-binding globulin (TBG) is a glycoprotein that has a higher affinity for T4 than for T3. Transthyretin is also a glycoprotein, but only carries T4, with hardly any affinity at all for T3. Finally, both hormones bind with a low affinity to serum albumin, but, due to the large availability of albumin, it has a high capacity.

The saturation of binding spots on thyronine-binding globulin (TBG) by endogenous T3 can be estimated by the triiodothyronine resin uptake test. The test is performed by taking a

blood sample, to which an excess of radioactive exogenous T3 is added, followed by a resin that also binds T3. A fraction of the radioactive T3 binds to sites on TBG not already occupied by endogenous thyroid hormone, and the remainder binds to the resin. The amount of labeled hormones bound to the resin is then subtracted from the total that was added, with the remainder thus being the amount that was bound to the unoccupied binding sites on TBG.[10]

Effects

T3 increases the

Na+/K+-ATPase (which normally constitutes a substantial fraction of total cellular ATP expenditure) without disrupting transmembrane ion balance.[11]
In general, it increases the turnover of different endogenous macromolecules by increasing their synthesis and degradation.

Skeletal growth

Thyroid hormones are essential for normal growth and skeletal maturation.

bone maturation.[11][12]

Protein

T3 stimulates the production of RNA polymerase I and II and, therefore, increases the rate of protein synthesis. It also increases the rate of protein degradation, and, in excess, the rate of protein degradation exceeds the rate of protein synthesis. In such situations, the body may go into negative ion balance.[further explanation needed]

Glucose

T3 potentiates the effects of the

β-adrenergic receptors on the metabolism of glucose. Therefore, it increases the rate of glycogen breakdown and glucose synthesis in gluconeogenesis.[citation needed
]

Lipids

T3 stimulates the breakdown of cholesterol and increases the number of LDL receptors, thereby increasing the rate of lipolysis.

Heart

T3 increases the heart rate and force of contraction, thus increasing

bounding pulse seen in hyperthyroidism.[citation needed] It also upregulates the thick filament protein myosin, which helps to increase contractility. A helpful clinical measure to assess contractility is the time between the QRS complex and the second heart sound. This is often decreased in hyperthyroidism
.

Development

T3 has profound effect upon the developing embryo and infants. It affects the lungs and influences the postnatal growth of the central nervous system. It stimulates the production of

neurotransmitters
, and the growth of axons. It is also important in the linear growth of bones.

Neurotransmitters

T3 may increase serotonin in the brain, in particular in the cerebral cortex, and down-regulate 5HT-2 receptors, based on studies in which T3 reversed learned helplessness in rats and physiological studies of the rat brain.[14]

Physiological function

Thyroid hormones act to increase protein turnover. This might serve an adaptive function in regard to long-term calorie restriction with adequate protein.[15][16] When calories are in short supply, reduction in protein turnover may ameliorate the effects of the shortage.

Measurement

Further information: Thyroid function tests

Triiodothyronine can be measured as free triiodothyronine, which is an indicator of triiodothyronine activity in the body. It can also be measured as total triiodothyronine, which also depends on the triiodothyronine that is bound to thyroxine-binding globulin.[17]

Uses

Treatment of depressive disorders

The addition of triiodothyronine to existing treatments such as

NOS whose treatment had previously been resistant to an average of 14 other medications. They found that 84% experienced improvement and 33% experienced full remission over a period of an average of 20.3[clarification needed] (standard deviation of 9.7). None of the patients experienced hypomania while on T3.[19]

Use as a fat loss supplement

3,5-Diiodo-L-thyronine and 3,3′-diiodo-L-thyronine are used as ingredients in certain over-the-counter fat-loss supplements, designed for bodybuilding. Several studies have shown that these compounds increase the metabolization of fatty acids and the burning of adipose fat tissue in rats.[20][21]

Alternative medicine

Triiodothyronine has been used to treat

thyroid function tests. The American Thyroid Association has raised concern that the prescribed treatment with triiodothyronine is potentially harmful.[22]

History

In 1950 Dr

radioactive iodine to study the physiology of thyroid hormone and applied chromatography to analyze radioiodinated proteins in human blood after radioiodine therapy. Gross and Leblond found an unknown radioactive compound in the blood of rats given radioactive iodine. The compound migrated close to thyroxine in chromatography and they initially named it 'unknown 1' . Around that time a group led by Jean Roche in Paris described a deiodinating activity in the sheep thyroid gland, raising the possibility that 'unknown 1' is the less iodinated analogue of T4, triiodothyronine.[23] In march of 1952 Gross & Pitt-Rivers published a paper in The Lancet titled "The identification of 3: 5: 3'-L-triiodothyronine in human plasma".[24]

See also

References

  1. ^ Bowen R (2010-07-24). "Physiologic Effects of Thyroid Hormones". Colorado State University. Retrieved 2013-09-29.
  2. ^ "How Your Thyroid Works – "A delicate Feedback Mechanism"". endocrineweb. 2012-01-30. Retrieved 2013-09-29.
  3. ^ "Cytomel (Liothyronine Sodium) Drug Information". RxList. 2011-01-03. Retrieved 2013-09-29.
  4. ^ Irizarry L (23 April 2014). "Thyroid Hormone Toxicity". Medscape. WedMD LLC. Retrieved 2 May 2014.
  5. LCCN 2004051158
    .
  6. PMID 25555216
    .
  7. PMID 2254444
    .
  8. PMID 18651367
    .
  9. ^ References used in image are found in image article in Commons:Commons:File:Thyroid_system.png#References.
  10. ^ triiodothyronine resin uptake test from Farlex Medical Dictionary, citing: Mosby's Medical Dictionary, 8th edition. 2009, Elsevier.
  11. ^
    OCLC 966608835
    .
  12. ^
    OCLC 1076268769
    .
  13. ^ "Thyroid physiology and tests of function". Anaesthetist.com.
  14. S2CID 43784239
    .
  15. PMID 16720655
    .
  16. PMID 12189585
    .
  17. ^ Military Obstetrics & Gynecology – Thyroid Function Tests In turn citing: Operational Medicine 2001, Health Care in Military Settings, NAVMED P-5139, May 1, 2001, Bureau of Medicine and Surgery, Department of the Navy, 2300 E Street NW, Washington, D.C., 20372-5300
  18. ^
    PMID 19108898
    .
  19. PMID 19215985
    .
  20. PMID 9461551
    .
  21. S2CID 1624615
    .
  22. ^ "ATA Statement on "Wilson's Syndrome"". American Thyroid Association. 24 May 2005.
  23. ^ Smith TS (2018-08-05). "HISTORY: Rosalind Pitt-Rivers, the co-discoverer of T3 hormone". Thyroid Patients Canada. Retrieved 2022-09-13.
  24. PMID 14898765
    .

External links
Retrieved from "https://en.wikipedia.org/w/index.php?title=Triiodothyronine&oldid=1157223925"