thyroxine
{{short description|Thyroid hormone}}
{{About|thyroxine as a hormone|its use as a medication|levothyroxine|the family of thyroid hormones|thyroid hormones}}
{{cs1 config|name-list-style=vanc|display-authors=6|display-editors=6}}
{{Chembox
| ImageFile = Thyroxine2.svg
| ImageFile1 = Thyroxine-3D-Sylocin.png
| ImageClass = skin-invert-image
| ImageSize =
| ImageAlt =
| IUPACName =
| OtherNames = O-(4-hydroxy-3,5-diiodophenyl)-3,5-diiodo-L-tyrosine, (-)-thyroxine, 3,3′,5,5′-tetraiodo-L-thyronine
| Section1 = {{Chembox Identifiers
| CASNo = 51-48-9
| CASNo_Comment = l enantiomer
| CASNo1 = 300-30-1
| CASNo1_Comment = DL
| ChEBI = 30660
| ChEMBL = 42115
| ChemSpiderID = 830
| EC_number = 206-088-9
| PubChem = 853
| UNII = QR0BV3BRIA
| StdInChI=1S/C15H11I4NO4/c16-8-4-7(5-9(17)13(8)21)24-14-10(18)1-6(2-11(14)19)3-12(20)15(22)23/h1-2,4-5,12,21H,3,20H2,(H,22,23)
| StdInChIKey = XUIIKFGFIJCVMT-UHFFFAOYSA-N
| SMILES = C1=C(C=C(C(=C1I)OC2=CC(=C(C(=C2)I)O)I)I)CC(C(=O)O)N
}}
| Section2 = {{Chembox Properties
| C=15|H=11|I=4|N=1|O=4
| MolarMass =
| Appearance = white solid
| Density =
| MeltingPtC = 235–236
| MeltingPt_notes =
| BoilingPt =
| BoilingPt_notes =
| Solubility = }}
| Section3 = {{Chembox Hazards
| MainHazards =
| FlashPt =
| AutoignitionPt = }}
}}
Thyroxine, also known as T4, is a hormone produced by the thyroid gland. It is the primary form of thyroid hormone found in the blood and acts as a prohormone of the more active thyroid hormone, triiodothyronine (T3).{{cite journal | vauthors = Li J, Bai L, Wei F, Wei M, Xiao Y, Yan W, Wei J | title = Effect of Addition of Thyroxine in the Treatment of Graves' Disease: A Systematic Review | journal = Frontiers in Endocrinology | volume = 11 | pages = 560157 | date = 2020 | pmid = 33569041 | pmc = 7868565 | doi = 10.3389/fendo.2020.560157 | doi-access = free }} Thyroxine and its active metabolites are essential for regulating metabolic rate, supporting heart and muscle function, promoting brain development, and maintaining bone health.{{cite journal | vauthors = Kim HY, Mohan S | title = Role and Mechanisms of Actions of Thyroid Hormone on the Skeletal Development | journal = Bone Research | volume = 1 | issue = 2 | pages = 146–161 | date = June 2013 | pmid = 26273499 | pmc = 4472099 | doi = 10.4248/BR201302004 }}{{cite journal | vauthors = Mullur R, Liu YY, Brent GA | title = Thyroid hormone regulation of metabolism | journal = Physiological Reviews | volume = 94 | issue = 2 | pages = 355–82 | date = April 2014 | pmid = 24692351 | pmc = 4044302 | doi = 10.1152/physrev.00030.2013 }}
Regulation
Thyroxine has a half-life of approximately one week and hence maintains relatively stable blood levels. Its production and release are controlled through a complex feedback loop involving the hypothalamus, pituitary gland, and thyroid gland. This regulatory system ensures that optimal hormone levels are maintained.{{cite book | vauthors = Rousset B, Dupuy C, Miot F, Dumont J | chapter = Chapter 2 Thyroid Hormone Synthesis And Secretion | date = September 2015 | veditors = Feingold KR, Anawalt B, Blackman MR, Boyce A, Chrousos G, Corpas E, de Herder WW, Dhatariya K, Dungan K, Hofland J, Kalra S, Kaltsas G, Kapoor N, Koch C, Kopp P, Korbonits M, Kovacs CS, Kuohung W, Laferrère B, Levy M, McGee EA, McLachlan R, New M, Purnell J, Sahay R, Shah AS, Singer F, Sperling MA, Stratakis CA, Trence DL, Wilson DP | title = Endotext [Internet] | location = South Dartmouth (MA) | publisher = MDText.com, Inc. | pmid = 25905405 | chapter-url = https://www.ncbi.nlm.nih.gov/books/NBK285550/ }}
Biosynthesis
File:Thyroxine biosynthesis.svg
Thyroxine biosynthesis is a multi-step process that occurs in follicular cell within the thyroid gland. The synthesis of thyroxine requires adequate iodine supply and appropriate hormonal control.{{cite journal | vauthors = Sorrenti S, Baldini E, Pironi D, Lauro A, D'Orazi V, Tartaglia F, Tripodi D, Lori E, Gagliardi F, Praticò M, Illuminati G, D'Andrea V, Palumbo P, Ulisse S | title = Iodine: Its Role in Thyroid Hormone Biosynthesis and Beyond | journal = Nutrients | volume = 13 | issue = 12 | date = December 2021 | page = 4469 | pmid = 34960019 | pmc = 8709459 | doi = 10.3390/nu13124469 | doi-access = free }}{{cite book | vauthors = Shahid MA, Ashraf MA, Sharma S | chapter = Physiology, Thyroid Hormone | date = June 2023 | title = StatPearls [Internet] | location = Treasure Island (FL) | publisher = StatPearls Publishing | pmid = 29763182 | chapter-url = https://www.ncbi.nlm.nih.gov/books/NBK500006/ }}
The process begins with the active uptake of iodide from the bloodstream by thyroid follicular cells through the sodium/iodide symporter (NIS) located in the basolateral membrane. Once inside the cell, iodide is transported to the follicular lumen, where it undergoes oxidation by the enzyme thyroid peroxidase (TPO) in the presence of hydrogen peroxide generated by the NADPH oxidase DUOX2. The oxidized iodine then iodinates tyrosyl residues of thyroglobulin (Tg), a glycoprotein synthesized by thyroid cells and stored in the follicular lumen. This process, known as organification, results in the formation of monoiodotyrosine (MIT) and diiodotyrosine (DIT) residues within the Tg molecule.
The final step in thyroxine synthesis involves the free radical mediated coupling of two DIT residues, catalyzed by TPO, to form T4 while still attached to the Tg backbone. When thyroid hormone is needed, Tg is internalized by thyrocytes, and proteolytic enzymes in lysosomes cleave the T4 from Tg, allowing for its release into the bloodstream. This intricate biosynthetic pathway is tightly regulated by thyroid-stimulating hormone (TSH) from the pituitary gland, which influences virtually every stage of thyroid hormone production.