Thyrotropin-releasing hormone

thyrotropin-releasing hormone
Structural formula of TRH
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
Pregnancy cat.  ?
Legal status  ?
Identifiers
ATC code  ?
ChEMBL CHEMBL1472 Y
Chemical data
Formula C16 H22 N6 O4
Mol. mass 362.38367

Thyrotropin-releasing hormone (TRH), also called thyrotropin-releasing factor (TRF), thyroliberin or protirelin, is a tropic, tripeptidal hormone that stimulates the release of thyroid-stimulating hormone and prolactin by the anterior pituitary. TRH has been used clinically for the treatment of spinocerebellar degeneration and disturbance of consciousness in humans.[1]

Contents

Synthesis

TRH is produced by the hypothalamus 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 -Glu-His-Pro-Gly-, flanked by di-basic peptides that are later processed through proteolysis to give the mature TRH molecule.

It 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] and excess levels inhibit dopamine, which stimulates the release of prolactin, which in turn decreases GnRH.

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

Clinical significance

It is used in pharmacology (brand name Relefact TRH) to test the response of the anterior pituitary gland.

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

A TRH test may be indicated if secondary hypothyroidism is suspected.

Related peptides

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

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

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. http://www.vivo.colostate.edu/hbooks/pathphys/endocrine/hypopit/tsh.html. 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. http://linkinghub.elsevier.com/retrieve/pii/0006-291X(69)90868-7. 
  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]" (in French). C.R. Hebd. Seances Acad. Sci., Ser. D, Sci. Nat. 269 (19): 1870–3. PMID 4983502. 
  7. ^ a b 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. http://nobelprize.org/nobel_prizes/medicine/laureates/1977/index.html. Retrieved 2009-03-04.