Summary: Thyrotropin-releasing hormone (TRH)

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Thyrotropin-releasing hormone Edit Wikipedia article

"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

Clinical data
Pregnancy cat.	?
Legal status	?
Identifiers
ATC code	V04CJ02
ChEMBL	CHEMBL1472^Y
Chemical data
Formula	C₁₆H₂₂N₆O₄
Mol. mass	362.38367 g/mol

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]

[edit] Synthesis

The system of the thyroid hormones T3 and T4.^[2]

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 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.

[edit] 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]

[edit] 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]

[edit] 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]

[edit] Side Effects

Side effects after intravenous TRH administration are minimal.^[13] Nausea, flushing, urinary urgency, and mild rise in blood pressure have been reported.^[14] After intrathecal administration, shaking, sweating, shivering, restlessness, and mild rise in blood pressure were observed.^[10]

[edit] Related peptides

Thyrotropin-releasing hormone (TRH)

Identifiers

Symbol

TRH

Available protein structures:
Pfam	structures
PDB	RCSB PDB; PDBe
PDBsum	structure summary

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

[edit] See also

Thyrotropin-releasing hormone receptor

[edit] References

^ 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.
^ References used in image are found in image article in Commons:Commons:File:Thyroid_system.png#References.
^ 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.
^ Bowen R (1998-09-20). "Thyroid-Stimulating Hormone". Pathophysiology of the Endocrine System. Colorado State University. Retrieved 2009-03-04.
^ 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.
^ 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]". C.R. Hebd. Seances Acad. Sci., Ser. D, Sci. Nat. (in French) 269 (19): 1870–3. PMID 4983502.
^ ^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.
^ "The Nobel Prize in Physiology or Medicine 1977". NobelPrize.org. Retrieved 2009-03-04.
^ CSID:554166, http://www.chemspider.com/Chemical-Structure.554166.html (accessed 00:54, Aug 29, 2012)
^ ^a ^b Marangell LB, George MS, Callahan AM, Ketter TA, Pazzaglia PJ, L'Herrou TA, Leverich GS, Post RM (March 1997). "Effects of intrathecal thyrotropin-releasing hormone (protirelin) in refractory depressed patients". Arch. Gen. Psychiatry 54 (3): 214–22. doi:10.1001/archpsyc.1997.01830150034007. PMID 9075462.
^ "Scientist developing anti-suicide nasal spray". ArmyTimes.com. 25 July 2012. Retrieved 2012-07-05.
^ "Army anti-suicide initiative brings $3 million to IU School of Medicine scientist’s research". Indiana University School of Medicine. July 24, 2012.
^ Prange AJ, Lara PP, Wilson IC, Alltop LB, Breese GR (November 1972). "Effects of thyrotropin-releasing hormone in depression". Lancet 2 (7785): 999–1002. doi:10.1016/S0140-6736(72)92407-5. PMID 4116985.
^ Borowski GD, Garofano CD, Rose LI, Levy RA (January 1984). "Blood pressure response to thyrotropin-releasing hormone in euthyroid subjects". J. Clin. Endocrinol. Metab. 58 (1): 197–200. doi:10.1210/jcem-58-1-197. PMID 6417153.

Endocrine system: hormones (Peptide hormones · Steroid hormones)

Endocrine
glands

Hypothalamic-
pituitary

Hypothalamus	GnRH · TRH · Dopamine · CRH · GHRH/Somatostatin · Melanin concentrating hormone

Posterior pituitary	Vasopressin · Oxytocin

Anterior pituitary	α (FSH FSHB, LH LHB, TSH TSHB, CGA) · Prolactin · POMC (CLIP, ACTH, MSH, Endorphins, Lipotropin) · GH

Adrenal axis

Adrenal cortex: aldosterone · cortisol · DHEA
Adrenal medulla: epinephrine · norepinephrine

Thyroid axis

Thyroid: thyroid hormone (T₃ and T₄) · calcitonin
Parathyroid: PTH

Gonadal axis

Testis: testosterone · AMH · inhibin

Ovary: estradiol · progesterone · activin and inhibin · relaxin (pregnancy)

Placenta: hCG · HPL · estrogen · progesterone

Islet-Acinar
Axis

Pancreas: glucagon · insulin · amylin · somatostatin · pancreatic polypeptide

Pineal gland

Pineal gland: melatonin

Non-end.
glands

Thymus: Thymosin (Thymosin α1, Thymosin beta) · Thymopoietin · Thymulin

Digestive system: Stomach: gastrin · ghrelin · Duodenum: CCK · Incretins (GIP, GLP-1) · secretin · motilin · VIP · Ileum: enteroglucagon · peptide YY · Liver/other: Insulin-like growth factor (IGF-1, IGF-2)

Adipose tissue: leptin · adiponectin · resistin

Skeleton: Osteocalcin

Kidney: JGA (renin) · peritubular cells (EPO) · calcitriol · prostaglandin

Heart: Natriuretic peptide (ANP, BNP)

M: END

anat/phys/devp/horm

noco (d)/cong/tumr, sysi/epon

proc, drug (A10/H1/H2/H3/H5)

Peptides: neuropeptides

Hormones

see hormones

Opioid peptides

Dynorphin	Big dynorphin Dynorphin A Dynorphin B

Endorphins	Beta-endorphin Alpha-endorphin Gamma-endorphin α-neo-endorphin β-neo-endorphin

Enkephalin	Met-enkephalin Leu-enkephalin

Others	Adrenorphin Amidorphin Leumorphin Nociceptin Opiorphin Spinorphin

Other
neuropeptides

Kinins	Bradykinin Tachykinins: mammal Substance P Neurokinin A Neurokinin B amphibian Kassinin Physalaemin

Neuromedins	B N S U

Other	Angiotensin Bombesin Calcitonin gene-related peptide Carnosine Cocaine and amphetamine regulated transcript Delta sleep-inducing peptide FMRFamide Galanin Galanin-like peptide Gastrin releasing peptide Neuropeptide S Neuropeptide Y Neurophysins Neurotensin Pancreatic polypeptide Pituitary adenylate cyclase activating peptide RVD-Hpα VGF

B trdu: iter (nrpl/grfl/cytl/horl), csrc (lgic, enzr, gprc, igsr, intg, nrpr/grfr/cytr), itra (adap, gbpr, mapk), calc, lipd; path (hedp, wntp, tgfp+mapp, notp, jakp, fsap, hipp, tlrp)

Others

Thyrotropin-releasing hormone (TRH) Provide feedback

This family consists of several thyrotropin-releasing hormone (TRH) proteins. Thyrotropin-Releasing Hormone (TRH; pyroGlu-His-Pro-NH2), originally isolated as a hypothalamic neuropeptide hormone, most likely acts also as a neuromodulator and/or neurotransmitter in the central nervous system (CNS). This interpretation is supported by the identification of a peptidase localised on the surface of neuronal cells which has been termed TRH-degrading ectoenzyme (TRH-DE) since it selectively inactivates TRH [1]. TRH has been used clinically for the treatment of spinocerebellar degeneration and disturbance of consciousness in humans [2].

Literature references

Heuer H, Schafer MK, Bauer K; , Acta Med Austriaca 1999;26:119-122.: Thyrotropin-releasing hormone (TRH), a signal peptide of the central nervous system. PUBMED:10526628 EPMC:10526628
Urayama A, Yamada S, Kimura R, Zhang J, Watanabe Y; , Life Sci 2002;72:601-607.: Neuroprotective effect and brain receptor binding of taltirelin, a novel thyrotropin-releasing hormone (TRH) analogue, in transient forebrain ischemia of C57BL/6J mice. PUBMED:12467901 EPMC:12467901

External database links

PANDIT:	PF05438
Pseudofam:	PF05438
SYSTERS:	TRH

This tab holds annotation information from the InterPro database.

InterPro entry IPR008857

This family consists of several thyrotropin-releasing hormone (TRH) proteins. Thyrotropin-Releasing Hormone (TRH; pyroGlu-His-Pro-NH2), originally isolated as a hypothalamic neuropeptide hormone, most likely acts also as a neuromodulator and/or neurotransmitter in the central nervous system (CNS). This interpretation is supported by the identification of a peptidase localised on the surface of neuronal cells which has been termed TRH-degrading ectoenzyme (TRH-DE) since it selectively inactivates TRH. TRH has been used clinically for the treatment of spinocerebellar degeneration and disturbance of consciousness in humans [PUBMED:12467901].

Gene Ontology

The mapping between Pfam and Gene Ontology is provided by InterPro. If you use this data please cite InterPro.

Cellular component	extracellular region (GO:0005576)
Molecular function	neuropeptide hormone activity (GO:0005184)
Biological process	hormone-mediated signaling pathway (GO:0009755)

Domain organisation

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Alignments

We store a range of different sequence alignments for families. As well as the seed alignment from which the family is built, we provide the full alignment, generated by searching the sequence database using the family HMM. We also generate alignments using four representative proteomes (RP) sets, the NCBI sequence database, and our metagenomics sequence database. More...

There are various ways to view or download the sequence alignments that we store. We provide several sequence viewers and a plain-text Stockholm-format file for download.

Alignment types

We make a range of alignments for each Pfam-A family:

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RP15/RP35/RP55/RP75: Representative Proteomes (RPs) at 15%, 35%, 55% and 75% co-membership thresholds
NCBI: alignment generated by searching the NCBI sequence database using the family HMM
meta: alignment generated by searching the metagenomics sequence database using the family HMM

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	Seed (9)	Full (77)	Representative proteomes				NCBI (66)	Meta (0)
	Seed (9)	Full (77)	RP15 (4)	RP35 (6)	RP55 (13)	RP75 (28)	NCBI (66)	Meta (0)
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HTML	View	View	View	View	View	View
PP/heatmap	₁	View	View	View	View	View
Pfam viewer	View	View

¹Cannot generate PP/Heatmap alignments for seeds; no PP data available

Key: available, not generated, — not available.

Format an alignment

	Seed (9)	Full (77)	Representative proteomes				NCBI (66)	Meta (0)
	Seed (9)	Full (77)	RP15 (4)	RP35 (6)	RP55 (13)	RP75 (28)	NCBI (66)	Meta (0)
Alignment:
Format:
Order:	Tree Alphabetical
Sequence:	Inserts lower case All upper case
Gaps:
Download/view:	Download View

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We make all of our alignments available in Stockholm format. You can download them here as raw, plain text files or as gzip-compressed files.

	Seed (9)	Full (77)	Representative proteomes				NCBI (66)	Meta (0)
	Seed (9)	Full (77)	RP15 (4)	RP35 (6)	RP55 (13)	RP75 (28)	NCBI (66)	Meta (0)
Raw Stockholm	Download	Download	Download	Download	Download	Download	Download
Gzipped	Download	Download	Download	Download	Download	Download	Download

You can also download a FASTA format file containing the full-length sequences for all sequences in the full alignment.

External links

MyHits provides a collection of tools to handle multiple sequence alignments. For example, one can refine a seed alignment (sequence addition or removal, re-alignment or manual edition) and then search databases for remote homologs using HMMER3.

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Trees

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Curation and family details

This section shows the detailed information about the Pfam family. You can see the definitions of many of the terms in this section in the glossary and a fuller explanation of the scoring system that we use in the scores section of the help pages.

Curation

Seed source:

Pfam-B_14384 (release 8.0)

Previous IDs:

none

Type:

Family

Author:

Moxon SJ

Number in seed:

9

Number in full:

77

Average length of the domain:

185.50 aa

Average identity of full alignment:

44 %

Average coverage of the sequence by the domain:

86.80 %

HMM information

HMM build commands:

build method: hmmbuild -o /dev/null HMM SEED

search method: hmmsearch -Z 23193494 -E 1000 --cpu 4 HMM pfamseq

Model details:

Parameter	Sequence	Domain
Gathering cut-off	27.8	27.8
Trusted cut-off	27.8	28.4
Noise cut-off	25.3	27.7

Model length:

212

Family (HMM) version:

7

Download:

download the raw HMM for this family

Species distribution

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Interactive tree

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Archea	Eukaryota
Bacteria	Other sequences
Viruses	Unclassified
Viroids	Unclassified sequence

Family: TRH (PF05438)

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