Thyrotropin-releasing hormone

2018-12-16T06:14:48Z

2600:100B:B108:B470:F11C:3313:DCCE:93D1: /* Related peptides */Need citation for "TRH belongs to a family of several thyrotropin-releasing hormones."

{{redirect|TRH}}
{{short description|hormone}}
{{infobox protein
| Name = thyrotropin-releasing hormone
| width = 200
| caption = [[Structural formula]] of TRH
| image = Thyrotropin-releasing hormone.svg
| HGNCid = 12298
| Symbol = TRH
| AltSymbols =
| EntrezGene = 7200
| OMIM = 275120
| RefSeq = NM_007117
| UniProt = P20396
| PDB =
| ECnumber =
| Chromosome = 3
| Arm = q
| Band = 13.3
| LocusSupplementaryData = -q21
}}

{{Drugbox
| IUPAC_name =

| pregnancy_AU = 
| pregnancy_US = 
| pregnancy_category =
| legal_AU = 
| legal_CA = 
| legal_UK = 
| legal_US = 
| legal_status =
| routes_of_administration =


| bioavailability =
| protein_bound =
| metabolism =
| elimination_half-life =
| excretion =


| IUPHAR_ligand = 2139
| CAS_number = 24305-27-9
| ATCvet =
| ATC_prefix = V04
| ATC_suffix = CJ02
| DrugBank =
| ChEBI = 35940
| ChEMBL_Ref = {{ebicite|correct|EBI}}
| ChEMBL = 1472
| PubChem = 638678
| ChemSpiderID = 554166


| C=16 | H=22 | N=6 | O=4
| molecular_weight = 362.38367 g/mol
| smiles = C1C[C@H](N(C1)C(=O)[C@H](CC2=CN=CN2)NC(=O)[C@@H]3CCC(=O)N3)C(=O)N
| StdInChI = 1S/C16H22N6O4/c17-14(24)12-2-1-5-22(12)16(26)11(6-9-7-18-8-19-9)21-15(25)10-3-4-13(23)20-10/h7-8,10-12H,1-6H2,(H2,17,24)(H,18,19)(H,20,23)(H,21,25)/t10-,11-,12-/m0/s1
| StdInChIKey = XNSAINXGIQZQOO-SRVKXCTJSA-N
}}

'''Thyrotropin-releasing hormone''' ('''TRH'''), also called '''thyrotropin-releasing factor''' ('''TRF''') or '''thyroliberin''', is a [[releasing hormone]], produced by the [[hypothalamus]], that stimulates the release of thyrotropin ([[thyroid-stimulating hormone]] or TSH) and [[prolactin]] from the [[anterior pituitary]]. It is a [[tropic hormone|tropic]], [[peptide hormone|tripeptidal hormone]].

TRH has been used clinically for the treatment of [[spinocerebellar degeneration]] and [[Neural correlates of consciousness#Global disorders of consciousness|disturbance of consciousness]] in humans.<ref name="PUB00011491">{{cite journal |vauthors=Zhang J, Watanabe Y, Yamada S, Urayama A, Kimura R |title=Neuroprotective effect and brain receptor binding of taltirelin, a novel thyrotropin-releasing hormone (TRH) analogue, in transient forebrain ischemia of C57BL/6J mice |journal=Life Sci. |volume=72 |issue=4–5 |pages=601–7 |year=2002 |pmid=12467901 |doi=10.1016/S0024-3205(02)02268-3}}</ref> Its [[pharmaceutical drug|pharmaceutical]] form is called '''protirelin''' ([[International Nonproprietary Name|INN]]) ({{IPAc-en|p|r|oʊ|ˈ|t|aɪ|r|ᵻ|l|ᵻ|n}}).

== Synthesis ==
[[File:Thyroid system.svg|thumb|250px|left|The system of the [[thyroid hormone]]s [[triiodothyronine|T3]] and [[thyroxine|T4]].<ref>References used in image are found in image article in Commons:[[Commons:File:Thyroid system.png#References]].</ref>]]

TRH is produced by the [[globe]] in medial neurons of the [[paraventricular nucleus]].<ref name="pmid2104587">{{cite journal | vauthors = Taylor T, Wondisford FE, Blaine T, Weintraub BD | title = The paraventricular nucleus of the hypothalamus has a major role in thyroid hormone feedback regulation of thyrotropin synthesis and secretion | journal = Endocrinology | volume = 126 | issue = 1 | pages = 317–24 |date=January 1990 | pmid = 2104587 | doi = 10.1210/endo-126-1-317| url = | issn = }}</ref> At the beginning, it is synthesized as a 242-amino acid precursor polypeptide that contains 6 copies of the sequence -Gln-His-Pro-Gly-, flanked by Lys-Arg or Arg-Arg sequences.

To produce the mature form, a series of enzymes are required. First, a protease cleaves to the C-terminal side of the flanking Lys-Arg or Arg-Arg. Second, a carboxypeptidase removes the Lys/Arg residues leaving Gly as the C-terminal residue. Then, this Gly is converted into an amide residue by a series of enzymes collectively known as peptidylglycine-alpha-amidating monooxygenase. Concurrently with these processing steps, the N-terminal Gln ([[glutamine]]) is converted into pyroglutamate (a cyclic residue). These multiple steps produce 6 copies of the mature TRH molecule per precursor molecule for human TRH (5 for mouse TRH).

Following secretion, TRH travels across the [[median eminence]] to the anterior pituitary gland via the [[hypophyseal portal system]] where it stimulates the release of [[thyroid-stimulating hormone]] from cells called [[thyrotrope]]s.<ref name="urlThyroid-Stimulating Hormone">{{cite web | url = http://www.vivo.colostate.edu/hbooks/pathphys/endocrine/hypopit/tsh.html | title = Thyroid-Stimulating Hormone | author = Bowen R | authorlink = | date = 1998-09-20 | work = Pathophysiology of the Endocrine System | publisher = Colorado State University | pages = | archiveurl = | archivedate = | accessdate = 2009-03-04}}</ref>

TRH can also be detected in other areas of the body including the [[gastrointestinal system]] and [[islets of Langerhans|pancreatic islets]], as well as in the brain.

== History ==

The seleke of TRH was first determined, and the hormone synthesized, by [[Roger Guillemin]] and [[Andrew V. Schally]] in 1969.<ref name="pmid4982117">{{cite journal | vauthors = Boler J, Enzmann F, Folkers K, Bowers CY, Schally AV | title = The identity of chemical and hormonal properties of the thyrotropin releasing hormone and pyroglutamyl-histidyl-proline amide | journal = Biochem. Biophys. Res. Commun. | volume = 37 | issue = 4 | pages = 705–10 |date=November 1969 | pmid = 4982117 | doi = 10.1016/0006-291X(69)90868-7| url = http://linkinghub.elsevier.com/retrieve/pii/0006-291X(69)90868-7 }}</ref><ref name="pmid4983502">{{cite journal | vauthors = Burgus R, Dunn TF, Desiderio D, Guillemin R | title = [Molecular structure of the hypothalamic hypophysiotropic TRF factor of ovine origin: mass spectrometry demonstration of the PCA-His-Pro-NH2 sequence] | language = French | journal = Comptes Rendus de l'Académie des Sciences, Série D | volume = 269 | issue = 19 | pages = 1870–3 |date=November 1969 | pmid = 4983502 | doi = | url = | issn = }}</ref> Both parties insisted their labs determined the sequence first: Schally first suggested the possibility in 1966, but abandoned it after Guillemin proposed TRH was not actually a peptide. Guillemin's chemist began concurring with these results in 1969, as NIH threatened to cut off funding for the project, leading both parties to return to work on synthesis.<ref name="isbn0-8039-0993-4">{{cite book | author = Woolgar, Steve | author2 = Latour, Bruno | authorlink = | editor = | others = | title = Laboratory life: the social construction of scientific facts | edition = | publisher = Sage Publications | location = Thousand Oaks | year = 1979 | seleke = | pages = | chapter = Chapter 3: The Case of TRF(H) | isbn = 0-8039-0993-4 | oclc = | doi = | url = | mohammed = }}</ref>

Schally and Guillemin shared the 1977 [[Nobel Prize in Medicine]] ''"for their discoveries concerning the peptide hormone production of the brain."''<ref name="urlMedicine 1977">{{cite web | url = http://nobelprize.org/nobel_prizes/medicine/laureates/1977/index.html | title = The Nobel Prize in Physiology or Medicine 1977 | author = | date = | work = | publisher = NobelPrize.org | pages = | sackor = | archivedate = | accessdate = 2009-03-04}}</ref> News accounts of their work often focused on their "fierce competition" and use of a very large amount of sheep and pig brains to locate the hormone.<ref name="isbn0-8039-0993-4"/>

== Chemical properties ==

Its molecular weight is 359.5 [[atomic mass unit|Da]]. Its tripeptide structure is: (pyro)Glu-His-Pro-NH<sub>2</sub>.
Its logp octanol/water is -2.46 <ref>CSID:554166, http://www.chemspider.com/Chemical-Structure.554166.html (accessed 00:54, Aug 29, 2012)</ref>

== Clinical significance ==
TRH is used clinically by intravenous injection (brand name Relefact TRH) to test the response of the [[anterior pituitary gland]]; this procedure is known as a [[TRH test]]. This is done as diagnostic test of [[thyroid]] disorders such as secondary [[hypothyroidism]] and in [[acromegaly]].

TRH has anti-depressant and anti-suicidal properties,<ref name="Marangell_1997"/> and in 2012 the U.S. Army awarded a research grant to develop a TRH nasal spray in order to prevent suicide amongst its ranks.<ref name="urlNasalSpray 1977">{{cite web | url = http://www.armytimes.com/news/2012/07/ap-anti-suicide-nasal-spray-research-072512/ | title = Scientist developing anti-suicide nasal spray | author = | date = 25 July 2012| work = | publisher = ArmyTimes.com | accessdate = 2012-07-05}}</ref><ref>{{cite web | url = http://communications.medicine.iu.edu/newsroom/stories/2012/army-anti-suicide-initiative-brings-3-million-to-iu-school-of-me/ | date = July 24, 2012 | title = Army anti-suicide initiative brings $3 million to IU School of Medicine scientist’s research | publisher = Indiana University School of Medicine}}</ref>

TRH has been shown in mice to be an anti-aging agent with a broad spectrum of activities that, because of their actions, suggest that TRH has a fundamental role in the regulation of metabolic and hormonal functions.<ref>Pierpaoli W.
, Aging-reversing properties of thyrotropin-releasing hormone.
, Curr Aging Sci. 2013 Feb;6(1):92-8.
</ref>

== Side effects ==

Side effects after intravenous TRH administration are minimal.<ref name="pmid4116985">{{cite journal | vauthors = Prange AJ, Lara PP, Wilson IC, Alltop LB, Breese GR | title = Effects of thyrotropin-releasing hormone in depression | journal = Lancet | volume = 2 | issue = 7785 | pages = 999–1002 |date=November 1972 | pmid = 4116985 | doi = 10.1016/S0140-6736(72)92407-5 }}</ref> Nausea, flushing, urinary urgency, and mild rise in blood pressure have been reported.<ref name="pmid6417153">{{cite journal | vauthors = Borowski GD, Garofano CD, Rose LI, Levy RA | title = Blood pressure response to thyrotropin-releasing hormone in euthyroid subjects | journal = J. Clin. Endocrinol. Metab. | volume = 58 | issue = 1 | pages = 197–200 |date=January 1984 | pmid = 6417153 | doi = 10.1210/jcem-58-1-197 }}</ref> After [[intrathecal]] administration, shaking, sweating, shivering, restlessness, and mild rise in blood pressure were observed.<ref name="Marangell_1997">{{cite journal | vauthors = Marangell LB, George MS, Callahan AM, Ketter TA, Pazzaglia PJ, L'Herrou TA, Leverich GS, Post RM | title = Effects of intrathecal thyrotropin-releasing hormone (protirelin) in refractory depressed patients | journal = Arch. Gen. Psychiatry | volume = 54 | issue = 3 | pages = 214–22 |date=March 1997 | pmid = 9075462 | doi = 10.1001/archpsyc.1997.01830150034007 }}</ref>

==Related peptides==
{{Pfam_box
| Symbol = TRH
| Name = Thyrotropin-releasing hormone (TRH)
| image =
| width =
| caption =
| Pfam= PF05438
| InterPro= IPR008857
| SMART=
| Prosite =
| SCOP =
| TCDB =
| OPM family=
| OPM protein=
| PDB=
}}

TRH belongs to a family of several thyrotropin-releasing hormones.{{Citation needed|reason=Need a source for this statement, and it should name at least two other such hormones to qualify as a "family"|date=December 2018}}

== See also ==
* [[Thyrotropin-releasing hormone receptor]]
* [[Hypothalamic–pituitary–prolactin axis]]

{{Clear}}

== References ==
{{reflist|35em}}

{{Hormones}}
{{Neuropeptides}}
{{Peptidergics}}

{{DEFAULTSORT:Thyrotropin-Releasing Hormone}}
[[Category:Hormones of the hypothalamus]]
[[Category:Hormones of the hypothalamic-pituitary-prolactin axis]]
[[Category:Peptide hormones]]
[[Category:Thyroid]]
[[Category:Hormones of the hypothalamus-pituitary-adrenal axis]]

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Thyrotropin-releasing hormone