Thyrotropin-releasing hormone

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

Structural formula of TRH

Identifiers
Symbol TRH
NCBI gene 7200
HGNC 12298
OMIM 275120
RefSeq NM_007117
UniProt P20396
Other data
Locus Chr. 3 q13.3-q21
Thyrotropin-releasing hormone
Clinical data
 V04CJ02 (WHO)
ATC code

Identifiers
 24305-27-9
CAS Number

 638678
PubChem CID

 2139
IUPHAR/BPS

 554166
ChemSpider

ChEBI  CHEBI:35940
 ChEMBL  ChEMBL1472 

 DTXSID0023533
CompTox Dashboard
(EPA)

ECHA InfoCard 100.041.934

Chemical and physical data
Formula C16H22N6O4
Molar mass 362.38367 g/mol g·mol−1
 Interactive image
3D model (JSmol)

SMILES[show]
InChI[show]

Thyrotropin-releasing hormone (TRH), is a hypophysiotropic hormone, produced by neurons

in the hypothalamus, that stimulates the release of thyroid-stimulating hormone (TSH) and
prolactin from the anterior pituitary.

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) (/proʊ
ˈtaɪrɪlɪn/).

Contents
 1 Synthesis and Release
 2 Structure
 3 History
 4 Clinical significance
 5 Side effects
 6 See also
 7 References
 8 External links

Synthesis and Release

The hypothalamic-pituitary-thyroid axis. TRH can be seen in green.

TRH is synthesized within parvocellular neurons of the paraventricular nucleus of the

hypothalamus.[2] It is translated 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).

TRH synthesizing neurons of the paraventricular nucleus project to the medial portion of the
external layer of the median eminence. Following secretion at the median eminence, TRH travels
to the anterior pituitary via the hypophyseal portal system where it binds to the TRH receptor
stimulating the release of thyroid-stimulating hormone from thyrotropes and prolactin from
lactotropes.[3] The half-life of TRH in the blood is approximately 6 minutes.

Structure
TRH is a tripeptide, with an amino acid sequence of pyroglutamyl-histidyl-proline amide.

History
The structure of TRH was first determined, and the hormone synthesized, by Roger Guillemin
and Andrew V. Schally in 1969.[4][5] 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.[6]

Schally and Guillemin shared the 1977 Nobel Prize in Medicine "for their discoveries
concerning the peptide hormone production of the brain."[7] 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.[6]

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,[8] 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.[9][10]

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.[11]

Side effects
Side effects after intravenous TRH administration are minimal.[12] Nausea, flushing, urinary
urgency, and mild rise in blood pressure have been reported.[13] After intrathecal administration,
shaking, sweating, shivering, restlessness, and mild rise in blood pressure were observed.[8]

Thyrotropin-releasing hormone (TRH)

Identifiers
Symbol TRH
Pfam PF05438
InterPro IPR008857
Available protein structures:

See also
 thyrotropin-releasing hormone receptor
 thyroid-stimulating hormone
 hypothalamic-pituitary thyroid axis
  hypothalamic–pituitary–prolactin axis

References