Protirelin

Protirelin

"TRH" redirects here. For other uses, see TRH (disambiguation).
thyrotropin-releasing hormone
Structural formula of TRH
Identifiers
Symbol TRH
Entrez HUGO OMIM RefSeq UniProt Locus q13.3-q21
Template:Drugbox

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

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 -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] and excess levels inhibit dopamine which will then stimulate 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. 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
Symbol TRH
Pfam InterPro IPR008857

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

See also


References