Thyrotropin-releasing hormone

"TRH" redirects here. For other uses, see TRH (disambiguation).
thyrotropin-releasing hormone

Identifiers
Symbol TRH
Entrez 7200
HUGO 12298
OMIM 275120
RefSeq NM_007117
UniProt P20396
Other data
Locus Chr. 3 q13.3-q21
Thyrotropin-releasing hormone
Clinical data
ATC code V04CJ02 (WHO)
Identifiers
CAS Number 24305-27-9
PubChem (CID) 638678
IUPHAR/BPS 2139
ChemSpider 554166
ChEBI CHEBI:35940
ChEMBL CHEMBL1472 YesY
ECHA InfoCard 100.041.934
Chemical and physical data
Formula C16H22N6O4
Molar mass 362.38367 g/mol
3D model (Jmol) Interactive image

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) (/proʊˈtaɪrᵻlᵻn/).

Synthesis

The system of the thyroid hormones T3 and T4.[2]

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 sequence 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]

Thyrotropin-releasing hormone (TRH)
Identifiers
Symbol TRH
Pfam PF05438
InterPro IPR008857

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. 1 2 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. 1 2 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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