関: prolactin-releasing hormone、protirelin tartrate、thyrotropin-releasing hormone

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出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2016/08/30 09:00:26」(JST)

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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.^[1] Its pharmaceutical form is called protirelin (INN) (/proʊˈtaɪrᵻlᵻn/).

Synthesis

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

TRH is produced by the globe 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]

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

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

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.
^ Pierpaoli W. , Aging-reversing properties of thyrotropin-releasing hormone. , Curr Aging Sci. 2013 Feb;6(1):92-8.
^ 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.

English Journal

Immune system and glucose metabolism interaction in schizophrenia: A chicken-egg dilemma.

Steiner J, Bernstein HG, Schiltz K, Müller UJ, Westphal S, Drexhage HA, Bogerts B.SourceDepartment of Psychiatry, University of Magdeburg, Magdeburg, Germany; Center for Behavioral Brain Sciences, Magdeburg, Germany. Electronic address: johann.steiner@med.ovgu.de.
Progress in neuro-psychopharmacology & biological psychiatry.Prog Neuropsychopharmacol Biol Psychiatry.2014 Jan 3;48:287-94. doi: 10.1016/j.pnpbp.2012.09.016. Epub 2012 Oct 17.
Impaired glucose metabolism and the development of metabolic syndrome contribute to a reduction in the average life expectancy of individuals with schizophrenia. It is unclear whether this association simply reflects an unhealthy lifestyle or whether weight gain and impaired glucose tolerance in pat
PMID 23085507

Retinoic X receptor subtypes exert differential effects on the regulation of Trh transcription.

Decherf S, Seugnet I, Becker N, Demeneix BA, Clerget-Froidevaux MS.SourceCNRS UMR 7221-USM 501, «Evolution of Endocrine Regulations», «Regulations, Development and Molecular Diversity» Department, Muséum National d'Histoire Naturelle, 57 rue Cuvier, CP 32, 75231 Paris Cedex 5, France.
Molecular and cellular endocrinology.Mol Cell Endocrinol.2013 Dec 5;381(1-2):115-23. doi: 10.1016/j.mce.2013.07.016. Epub 2013 Jul 26.
How Retinoid X receptors (RXR) and thyroid hormone receptors (TR) interact on negative TREs and whether RXR subtype specificity is determinant in such regulations is unknown. In a set of functional studies, we analyzed RXR subtype effects in T3-dependent repression of hypothalamic thyrotropin-releas
PMID 23896434

Dynamic Kisspeptin Receptor Trafficking Modulates Kisspeptin-mediated Calcium Signaling.

Min L, Soltis K, Reis AC, Xu S, Kuohung W, Jain M, Carroll RS, Kaiser UB.Source1Division of Endocrinology, Diabetes and Hypertension, Brigham and Women's Hospital, Harvard Medical School, 221 Longwood Ave, Boston, MA 02115.
Molecular endocrinology (Baltimore, Md.).Mol Endocrinol.2013 Dec 2. [Epub ahead of print]
Kisspeptin receptor (KISS1R) signaling plays a critical role in the regulation of reproduction. We investigated the role of kisspeptin-stimulated KISS1R internalization, recycling, and degradation in the modulation of KISS1R signaling. Kisspeptin stimulation of CHO or GT1-7 cells expressing KISS1R r
PMID 24295737

Japanese Journal

重症熱中症急性期にMRI拡散強調像にて小脳皮質の高信号を捉えた1例

藤岡祐介,安井敬三,長谷川康博 [他],高橋昭,祖父江元
臨床神経学 49(10), 634-640, 2009-10-01
NAID 10026290475

悪性症候群後に小脳性運動失調をきたした1例

永嶌朋久,宮本敏雄,森川将行,根來秀樹,岸本年史
Journal of Nara Medical Association 57(2/3), 67-72, 2006-06-30
… We speculated that exposure to abnormal high temperature damaged Purkinje cells in the cerebellum and started to administer tartaric acid protirelin intravenously. …
NAID 110004997558

妊娠２５週から抗癌剤治療し，生児を得た悪性リンパ腫合併妊娠の１症例

益弘和雄,小林克弥,松本公一,前田哲雄,今井史郎,青野豊文,森本靖彦,川本豊,中川雅史
産婦人科の進歩 53(4), 323-328, 2001
… 化学療法中の胎児評価として, daily NST, 超音波診断層法検査, Pulse Doppler検査を適宜行い, また早産に備えて胎児の肺成熟を促すためにTRH製剤(protirelin tartrate), dexamethasoneを母体に投与した. …
NAID 130001223833

「プロチレリン」

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

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
Chemical data
Formula	C16H22N6O4
Molar 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
	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

　　[★]

英: protirelin
化: 酒石酸プロチレリン protirelin tartrate、プロチレリン酒石酸塩
商: TRH注、ヒシダリン、ヒルトニン、ヒルロック、ボグニン

「protirelin tartrate」

　　[★]

酒石酸プロチレリン

関: protirelin

[PUB00011491-1] 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.

[2] References used in image are found in image article in Commons:Commons:File:Thyroid system.png#References.

[pmid2104587-3] 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.

[urlThyroid-Stimulating_Hormone-4] Bowen R (1998-09-20). "Thyroid-Stimulating Hormone". Pathophysiology of the Endocrine System. Colorado State University. Retrieved 2009-03-04.

[pmid4982117-5] 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.

[pmid4983502-6] 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.

[isbn0-8039-0993-4-7] 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.

[urlMedicine_1977-8] "The Nobel Prize in Physiology or Medicine 1977". NobelPrize.org. Retrieved 2009-03-04.

[9] CSID:554166, http://www.chemspider.com/Chemical-Structure.554166.html (accessed 00:54, Aug 29, 2012)

[Marangell_1997-10] 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.

[urlNasalSpray_1977-11] "Scientist developing anti-suicide nasal spray". ArmyTimes.com. 25 July 2012. Retrieved 2012-07-05.

[12] "Army anti-suicide initiative brings $3 million to IU School of Medicine scientist's research". Indiana University School of Medicine. July 24, 2012.

[13] Pierpaoli W. , Aging-reversing properties of thyrotropin-releasing hormone. , Curr Aging Sci. 2013 Feb;6(1):92-8.

[pmid4116985-14] 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.

[pmid6417153-15] 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.

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protirelin