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__NOTOC__
{{redirect|TRH}}
{{protein
{{infobox protein
| Name = thyrotropin-releasing hormone
| Name = thyrotropin-releasing hormone
| width = 200
| caption = [[Structural formula]] of TRH
| caption = [[Structural formula]] of TRH
| image = Thyrotropin-releasing hormone_svg.png
| image = Thyrotropin-releasing hormone.svg
| width = 200
| HGNCid = 12298
| HGNCid = 12298
| Symbol = TRH
| Symbol = TRH
Line 19: Line 19:
| LocusSupplementaryData = -q21
| LocusSupplementaryData = -q21
}}
}}
{{SI}}
{{GS}}


==Overview==
{{Drugbox
'''Thyrotropin-releasing hormone''' ('''TRH'''), also called '''thyrotropin-releasing factor''' ('''TRF'''), '''thyroliberin''' or '''protirelin''', is a [[peptide hormone|tripeptide hormone]] that stimulates the release of [[thyroid-stimulating hormone]] and [[prolactin]] by the [[anterior pituitary]].  
| IUPAC_name =  
<!--Clinical data-->
| pregnancy_AU = <!-- A / B1 / B2 / B3 / C / D / X -->
| pregnancy_US = <!-- A / B            / C / D / X -->
| pregnancy_category =
| legal_AU = <!-- S2, S3, S4, S5, S6, S7, S8, S9 or Unscheduled-->
| legal_CA = <!-- OTC, Rx-only, Schedule I, II, III, IV, V, VI, VII, VIII -->
| legal_UK = <!-- GSL, P, POM, CD, CD Lic, CD POM, CD No Reg POM, CD (Benz) POM, CD (Anab) POM or CD Inv POM -->
| legal_US = <!-- OTC / Rx-only / Schedule I, II, III, IV, V -->
| legal_status =
| routes_of_administration =
 
<!--Pharmacokinetic data-->
| bioavailability =
| protein_bound =
| metabolism =
| elimination_half-life =
| excretion =
 
<!--Identifiers-->
| 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
 
<!--Chemical data-->
| 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.


==Production==
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).
TRH is produced by the [[hypothalamus]], near the [[paraventricular nucleus]].<ref>{{cite journal |author=Taylor T, Wondisford F, Blaine T, Weintraub B |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 |year=1990 |pmid=2104587}}</ref>


It travels across the [[median eminence]] to the pituitary via the [[hypophyseal portal system]]. It is released from cells called [[thyrotropes]].<ref>http://www.vivo.colostate.edu/hbooks/pathphys/endocrine/hypopit/tsh.html</ref>
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>


In addition to the brain, TRH can also be detected in other areas of the body including the [[gastrointestinal system]] and [[islets of Langerhans|pancreatic islets]].
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==
== History ==
The sequence of TRH was first determined and the hormone synthesized by [[Roger Guillemin]] and [[Andrew V. Schally]] in 1969.<ref>Boler J, Enzmann F, Folkers K, Bowers CY, Schally AV. ''The identity of chemical and hormonal properties of the thyrotropin releasing hormone and pyroglutamyl-histidyl-proline amide.'' Biochem Biophys Res Commun 1969;37:705-10. PMID 4982117</ref><ref>Burgus R, Dunn TF, Desiderio D, Guillemin R. ''Molecular structure of the hypothalamic hypophysiotropic TRF factor of ovine origin: mass spectrometry demonstration of the PCA-His-Pro-NH2 sequence.'' Comptes Rendus hebdomadaires des Séances de l’Académie des Sciences 1969;269:1870–1873. <!--not indexed for medline!--></ref>


==Chemical properties==
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 = C.R. Hebd. Seances Acad. Sci., Ser. D, Sci. Nat. | 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>
Its molecular weight is 359.5 Da.  


Its structure is: (pyro)Glu-His-Pro-NH<sub>2</sub>
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"/>


==Clinical significance==
== Chemical properties ==
It is used in pharmacology (brand name Relefact TRH&reg;) to test the response of the [[anterior pituitary gland]].


Medical preparations of TRH are used in diagnostic tests of [[thyroid]] disorders and in [[acromegaly]].
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>


In 1998, a recombinant form of the hormone was approved by FDA, Thyrogen&reg; (thyrotropin alfa), and is used in the detection of residual or recurrent thyroid cancer. (http://www.fda.gov/Cder/consumerinfo/druginfo/thyrogen.HTM)
== 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]].


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


==References==
{{Clear}}
<references/>
 
[http://home.myspace.com/index.cfm?fuseaction=user&MyToken=b6edf1ea-9cd2-42fd-b6d5-2cad8b549b30]
[http://www.fda.gov/Cder/consumerinfo/druginfo/thyrogen.HTM]


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


{{Template:Hormones}}
{{Hormones}}
{{Neuropeptides}}
{{Neuropeptides}}
{{Peptidergics}}


{{DEFAULTSORT:Thyrotropin-Releasing Hormone}}


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[[it:TRH (ormone)]]
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[[ja:甲状腺刺激ホルモン放出ホルモン]]
[[pl:Tyreoliberyna]]
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Revision as of 08:02, 9 August 2017

Lua error in Module:Redirect at line 65: could not parse redirect on page "TRH".

thyrotropin-releasing hormone
File:Thyrotropin-releasing hormone.svg
Identifiers
SymbolTRH
Entrez7200
HUGO12298
OMIM275120
RefSeqNM_007117
UniProtP20396
Other data
LocusChr. 3 q13.3-q21
Thyrotropin-releasing hormone
Clinical data
ATC code
Identifiers
CAS Number
PubChem CID
IUPHAR/BPS
ChemSpider
ChEBI
ChEMBL
E number{{#property:P628}}
ECHA InfoCard{{#property:P2566}}Lua error in Module:EditAtWikidata at line 36: attempt to index field 'wikibase' (a nil value).
Chemical and physical data
FormulaC16H22N6O4
Molar mass362.38367 g/mol
3D model (JSmol)

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, tripeptidal hormone.

TRH has been used clinically for the treatment of spinocerebellar degeneration and disturbance of consciousness in humans.[1] Its pharmaceutical form is called protirelin (INN) (/proʊˈtaɪrɪlɪn/).

Synthesis

File:Thyroid system.svg

TRH is produced by the globe in medial neurons of the paraventricular nucleus.[3] 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 thyrotropes.[4]

TRH can also be detected in other areas of the body including the gastrointestinal system and 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.[5][6] 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.[7]

Schally and Guillemin shared the 1977 Nobel Prize in Medicine "for their discoveries concerning the peptide hormone production of the brain."[8] 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.[7]

Chemical properties

Its molecular weight is 359.5 Da. Its tripeptide structure is: (pyro)Glu-His-Pro-NH2. Its logp octanol/water is -2.46 [9]

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,[10] 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.[11][12]

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.[13]

Side effects

Side effects after intravenous TRH administration are minimal.[14] Nausea, flushing, urinary urgency, and mild rise in blood pressure have been reported.[15] After intrathecal administration, shaking, sweating, shivering, restlessness, and mild rise in blood pressure were observed.[10]

Related peptides

Thyrotropin-releasing hormone (TRH)
Identifiers
SymbolTRH
PfamPF05438
InterProIPR008857

TRH belongs to a family of several thyrotropin-releasing hormones.

See also

References

  1. ↑ Zhang J, Watanabe Y, Yamada S, Urayama A, Kimura R (2002). "Neuroprotective effect and brain receptor binding of taltirelin, a novel thyrotropin-releasing hormone (TRH) analogue, in transient forebrain ischemia of C57BL/6J mice". Life Sci. 72 (4–5): 601–7. doi:10.1016/S0024-3205(02)02268-3. PMID 12467901.
  2. ↑ References used in image are found in image article in Commons:Commons:File:Thyroid system.png#References.
  3. ↑ Taylor T, Wondisford FE, Blaine T, Weintraub BD (January 1990). "The paraventricular nucleus of the hypothalamus has a major role in thyroid hormone feedback regulation of thyrotropin synthesis and secretion". Endocrinology. 126 (1): 317–24. doi:10.1210/endo-126-1-317. PMID 2104587.
  4. ↑ Bowen R (1998-09-20). "Thyroid-Stimulating Hormone". Pathophysiology of the Endocrine System. Colorado State University. Retrieved 2009-03-04.
  5. ↑ Boler J, Enzmann F, Folkers K, Bowers CY, Schally AV (November 1969). "The identity of chemical and hormonal properties of the thyrotropin releasing hormone and pyroglutamyl-histidyl-proline amide". Biochem. Biophys. Res. Commun. 37 (4): 705–10. doi:10.1016/0006-291X(69)90868-7. PMID 4982117.
  6. ↑ Burgus R, Dunn TF, Desiderio D, Guillemin R (November 1969). "[Molecular structure of the hypothalamic hypophysiotropic TRF factor of ovine origin: mass spectrometry demonstration of the PCA-His-Pro-NH2 sequence]". C.R. Hebd. Seances Acad. Sci., Ser. D, Sci. Nat. (in French). 269 (19): 1870–3. PMID 4983502.
  7. ↑ 7.0 7.1 Woolgar, Steve; Latour, Bruno (1979). "Chapter 3: The Case of TRF(H)". Laboratory life: the social construction of scientific facts. Thousand Oaks: Sage Publications. ISBN 0-8039-0993-4.
  8. ↑ "The Nobel Prize in Physiology or Medicine 1977". NobelPrize.org. Retrieved 2009-03-04.
  9. ↑ CSID:554166, http://www.chemspider.com/Chemical-Structure.554166.html (accessed 00:54, Aug 29, 2012)
  10. ↑ 10.0 10.1 Marangell LB, George MS, Callahan AM, Ketter TA, Pazzaglia PJ, L'Herrou TA, Leverich GS, Post RM (March 1997). "Effects of intrathecal thyrotropin-releasing hormone (protirelin) in refractory depressed patients". Arch. Gen. Psychiatry. 54 (3): 214–22. doi:10.1001/archpsyc.1997.01830150034007. PMID 9075462.
  11. ↑ "Scientist developing anti-suicide nasal spray". ArmyTimes.com. 25 July 2012. Retrieved 2012-07-05.
  12. ↑ "Army anti-suicide initiative brings $3 million to IU School of Medicine scientist's research". Indiana University School of Medicine. July 24, 2012.
  13. ↑ Pierpaoli W. , Aging-reversing properties of thyrotropin-releasing hormone. , Curr Aging Sci. 2013 Feb;6(1):92-8.
  14. ↑ Prange AJ, Lara PP, Wilson IC, Alltop LB, Breese GR (November 1972). "Effects of thyrotropin-releasing hormone in depression". Lancet. 2 (7785): 999–1002. doi:10.1016/S0140-6736(72)92407-5. PMID 4116985.
  15. ↑ Borowski GD, Garofano CD, Rose LI, Levy RA (January 1984). "Blood pressure response to thyrotropin-releasing hormone in euthyroid subjects". J. Clin. Endocrinol. Metab. 58 (1): 197–200. doi:10.1210/jcem-58-1-197. PMID 6417153.
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