Thyrotropin-releasing hormone.html



Structural formula of TRH
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 (TRH), also called thyrotropin-releasing factor (TRF), thyroliberin or protirelin, is a tropic tripeptide hormone that stimulates the release of thyroid-stimulating hormone and prolactin by the anterior pituitary.

Production

TRH is produced by the hypothalamus in medial neurons of the paraventricular nucleus.¹ Initially, 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.²

In addition to the brain, TRH can also be detected in other areas of the body including the gastrointestinal system and pancreatic islets.

History

The sequence of TRH was first determined and the hormone synthesized by Roger Guillemin and Andrew V. Schally in 1969.³⁴ Both parties insist their labs determined it 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.⁵

Half of the 1977 Nobel Prize in Medicine was awarded to Schally and Guillemin "for their discoveries concerning the peptide hormone production of the brain."⁶ News accounts of their work often focus on their "fierce competition" and use of tons 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. Some patients may have low levels of circulating thyroid hormones and secondary hypothyroidism as a result of damage to the hypothalamic or pituitary control mechanisms that regulate thyroid function. The hypothalamus makes a small hormone called TRH that directs the synthesis and secretion of TSH from the pituitary gland. If these normal regulatory mechanisms are interrupted, the pituitary may not be able to produce appropriate levels of TSH and levels of thyroid hormones may decline, although the TSH remains appropriately normal. The TRH test involves administration of a small amount of TRH intravenously, following which levels of TSH will be measured at several subsequent time points using samples of blood taken from a peripheral vein. Patients with normal function of the hypothalamic-pituitary axis (HPA) respond by increasing the levels of TSH following TRH injection. Patients with compromised HPA function may exhibit a delayed, blunted, or absent response to TRH administration. TRH may cause nausea, vomiting and some patients experience an urge to urinate. Rarely, TRH may cause blood vessel constriction leading to hemorrhage in patients with pre-existing pituitary tumors. Accordingly, patients should be advised about the risks, albeit rare, of TRH testing.[1]

See also

• Thyrotropin-releasing hormone receptor

References

1. ^ Taylor T, Wondisford F, Blaine T, Weintraub B (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. PMID 2104587. 
2. ^ Thyroid-Stimulating Hormone
3. ^ 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
4. ^ 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.
5. ^ ^{a b} "The Construction of a Fact: The Case of TRF(H)", ch. 3 in Bruno Latour and Steve Woolgar, Laboratory Life: The Construction of Scientific Facts (1979)
6. ^ http://nobelprize.org/nobel_prizes/medicine/laureates/1977/index.html
7. ^ ⁵ at 149ff. (Esp. see notes for additional accounts.)