Thyrotropin-releasing hormone

"TRH" redirects here. For other uses, see TRH (disambiguation).

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

Identifiers
CAS Number	24305-27-9
ATC code	V04CJ02 (WHO)
PubChem	CID: 638678
IUPHAR/BPS	2139
ChemSpider	554166
ChEBI	CHEBI:35940
ChEMBL	CHEMBL1472 Y
Chemical data
Formula	C16H22N6O4
Molecular mass	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
InChI InChI=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 Key: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, tripeptidal hormone.

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

Synthesis

The system of the thyroid hormones T3 and T4.

TRH is produced by the hypothalamus in medial neurons of the paraventricular nucleus. 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.

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. 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.

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

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

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, 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.

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.

Side Effects

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

Related peptides

Thyrotropin-releasing hormone (TRH)
Identifiers
Symbol	TRH
Pfam	PF05438
InterPro	IPR008857
Available protein structures: Pfam structures PDB RCSB PDB; PDBe; PDBj PDBsum structure summary

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

See also

• Thyrotropin-releasing hormone receptor