Relaxin

2017-11-29T06:45:18Z

2605:E000:8750:ED00:7830:91C0:5C0:A9B2: /* Structure */Added content

{{for|the [[Miles Davis]] album|Relaxin' with the Miles Davis Quintet}}
{{infobox protein
| Name = Relaxin 1
| caption =
| image = relaxin.png
| width =
| HGNCid = 10026
| Symbol = RLN1
| AltSymbols = H1
| EntrezGene = 6013
| OMIM = 179730
| RefSeq = NM_006911
| UniProt = P04808
| PDB =
| ECnumber =
| Chromosome = 9
| Arm = q
| Band = ter
| LocusSupplementaryData = -q12
}}
{{infobox protein
| Name = Relaxin 2
| caption =
| image =
| width =
| HGNCid = 10027
| Symbol = RLN2
| AltSymbols = H2, RLXH2, bA12D24.1.1, bA12D24.1.2
| EntrezGene = 6019
| OMIM = 179740
| RefSeq = NM_134441
| UniProt = P04090
| PDB = 6RLX
| ECnumber =
| Chromosome = 9
| Arm = q
| Band = ter
| LocusSupplementaryData = -q12
}}
{{infobox protein
| Name = Relaxin 3
| caption =
| image =
| width =
| HGNCid = 17135
| Symbol = RLN3
| AltSymbols = ZINS4, RXN3, H3
| EntrezGene = 117579
| OMIM = 606855
| RefSeq = NM_080864
| UniProt = Q8WXF3
| PDB =
| ECnumber =
| Chromosome = 19
| Arm = p
| Band = 13.3
| LocusSupplementaryData =
}}

'''Relaxin''' is a [[protein]] [[hormone]] of about 6000 Da<ref name="pmid9112071">{{cite journal | author = Bani D | title = Relaxin: a pleiotropic hormone. | journal = General pharmacology | volume = 28 | issue = 1 | pages = 13–22 | date = January 1997 | pmid = 9112071 | doi=10.1016/s0306-3623(96)00171-1}}</ref> first described in 1926 by Frederick Hisaw.<ref name="urlIf a Gopher Can Do It ... - TIME">{{cite web | url = http://www.time.com/time/magazine/article/0,9171,796530,00.html | title = If a Gopher Can Do It ... | date = 1944-04-10 | work = | publisher = Time Magazine | pages = | language = | archiveurl = | archivedate = | quote = | accessdate = 2009-05-20}}</ref><ref name="pmid11231378">{{cite journal |vauthors=Becker GJ, Hewitson TD | title = Relaxin and renal fibrosis | journal = Kidney Int. | volume = 59 | issue = 3 | pages = 1184–5 | date = March 2001 | pmid = 11231378 | doi = 10.1046/j.1523-1755.2001.0590031184.x | url = }}</ref>

The relaxin-like peptide family belongs in the insulin superfamily and consists of 7 peptides of high structural but low sequence similarity; relaxin-1 ([[RLN1]]), 2 ([[RLN2]]) and 3 ([[RLN3]]), and the insulin-like (INSL) peptides, [[INSL3]], [[INSL4]], [[INSL5]] and [[INSL6]]. The functions of relaxin-3, INSL4, INSL5, INSL6 remain uncharacterised.<ref name="pmid15707501">{{cite journal |vauthors=Wilkinson TN, Speed TP, Tregear GW, Bathgate RA | title = Evolution of the relaxin-like peptide family | journal = BMC Evolutionary Biology | volume = 5 | pages = 14 | date = February 2005 | pmid = 15707501 | pmc = 551602 | doi = 10.1186/1471-2148-5-14 | url = }}</ref>

==Synthesis==
In the female, it is produced by the [[corpus luteum]] of the [[ovary]], the [[breast]] and, during [[pregnancy]], also by the [[placenta]], [[chorion]], and [[decidua]].

In the male, it is produced in the prostate and is present in human semen.<ref name="pmid2011710">{{cite journal | author = MacLennan AH | title = The role of the hormone relaxin in human reproduction and pelvic girdle relaxation | journal = Scandinavian journal of rheumatology. Supplement | volume = 88 | issue = | pages = 7–15 | year = 1991 | pmid = 2011710 | doi = | url = }}</ref>

==Structure==
{{See also|Insulin/IGF/Relaxin family}}
Structurally, relaxin is a [[heterodimer]] of two peptide chains of 24 and 29 [[amino acid]]s linked by [[disulfide]] bridges, and it appears related to [[insulin]].

Relaxin is produced from its [[prohormone]], "prorelaxin", by splitting off one additional peptide chain reaction.

==Function==

===In humans===

In females, relaxin is produced mainly by the corpus luteum, in both pregnant <ref name="pmid9112071" /> and nonpregnant<ref name="pmid9112071" /> females; it rises to a peak within approximately 14 days of [[ovulation]], and then declines in the absence of pregnancy, resulting in [[menstruation]] {{Citation needed|date=August 2013}}). During the first trimester of pregnancy, levels rise and additional relaxin is produced by the decidua. Relaxin's peak is reached during the 14 weeks of the first trimester and at delivery. It is known to mediate the hemodynamic changes that occur during pregnancy, such as increased cardiac output, increased renal blood flow, and increased arterial compliance. It also relaxes other pelvic ligaments.<ref name="pmid21613576">{{cite journal | author = Conrad KP | title = Maternal vasodilation in pregnancy: the emerging role of relaxin | journal = Am. J. Physiol. Regul. Integr. Comp. Physiol. | volume = 301 | issue = 2 | pages = R267–75 | date = August 2011 | pmid = 21613576 | pmc = 3154715 | doi = 10.1152/ajpregu.00156.2011 }}</ref> It is believed to soften the [[pubic symphysis]].

In males, relaxin enhances motility of sperm in semen.<ref name="pmid2497805">{{cite journal | author = Weiss G | title = Relaxin in the male | journal = Biol. Reprod. | volume = 40 | issue = 2 | pages = 197–200 | date = February 1989 | pmid = 2497805 | doi = 10.1095/biolreprod40.2.197 | url = http://www.biolreprod.org/cgi/reprint/40/2/197 }}</ref>

===In other animals===
In animals, relaxin widens the [[pubic bone]] and facilitates [[childbirth|labor]]; it also softens the [[cervix]] (cervical ripening), and relaxes the uterine musculature. Thus, for a long time, relaxin was looked at as a pregnancy hormone. However, its significance may reach much further. Relaxin affects [[collagen]] metabolism, inhibiting collagen synthesis and enhancing its breakdown by increasing [[matrix metalloproteinase]]s.<ref>{{cite journal |vauthors=Mookerjee I, Solly NR, Royce SG, Tregear GW, Samuel CS, Tang ML | title = Endogenous relaxin regulates collagen deposition in an animal model of allergic airway disease | journal = Endocrinology | volume = 147 | issue = 2 | pages = 754–61 | year = 2006 | pmid = 16254028 | doi = 10.1210/en.2005-1006 }}</ref> It also enhances [[angiogenesis]] and is a potent renal [[vasodilator]].

In the European Rabbit, (''Oryctolagus cuniculus''), relaxin<ref name="Arroyo_2012">{{cite journal | vauthors = Arroyo JI, Hoffmann FG, Opazo JC | title = Gene duplication and positive selection explains unusual physiological roles of the relaxin gene in the European rabbit | journal = Journal of Molecular Evolution | volume = 74 | issue = 1-2 | pages = 52–60 | year = 2012 | pmid = 22354201 | doi = 10.1007/s00239-012-9487-2 }}</ref> is associated with squamous differentiation and is expressed in tracheobronchial epithelial cells as opposed to being involved with reproduction.

==Receptors==
Relaxin interacts with the [[relaxin receptor]] LGR7 ([[RXFP1]]) and LGR8 ([[RXFP2]]), which belong to the [[G protein-coupled receptor]] superfamily.<ref>{{cite journal |vauthors=Hsu SY, Nakabayashi K, Nishi S, Kumagai J, Kudo M, Sherwood OD, Hsueh AJ | title = Activation of orphan receptors by the hormone relaxin | journal = Science | volume = 295 | issue = 5555 | pages = 674–6 | year = 2002 | pmid = 11809971 | doi = 10.1126/science.1065654 }}</ref> They contain a heptahelical [[Transmembrane helix|transmembrane domain]] and a large glycosylated ectodomain, distantly related to the receptors for the glycoproteohormones, such as the [[LH-receptor]] or [[FSH-receptor]].

Relaxin receptors have been found in the [[heart]], [[smooth muscle]], the [[connective tissue]], and central and [[autonomous nervous system]].

==Disorders==
Specific disorders related to relaxin have not been described, yet a link to [[scleroderma]] and [[fibromyalgia]] has been suggested.<ref>{{cite journal |vauthors=Van Der Westhuizen ET, Summers RJ, Halls ML, Bathgate RA, Sexton PM | title = Relaxin receptors--new drug targets for multiple disease states | journal = Curr Drug Targets | volume = 8 | issue = 1 | pages = 91–104 | year = 2007 | pmid = 17266534 | doi = 10.2174/138945007779315650 }}</ref>

==Pharmacological targets==

A recombinant form of human relaxin-2 has been developed as investigational drug RLX030 ([[serelaxin]]).

== Evolution ==
Relaxin 1 and Relaxin 2 arose from the duplication of a proto-RLN gene between 44.2 and 29.6 million years ago in the last common ancestor of catarrhine primates.<ref name="Arroyo_2014">{{cite journal | vauthors = Arroyo JI, Hoffmann FG, Opazo JC | title = Evolution of the relaxin/insulin-like gene family in anthropoid primates | journal = Genome Biology and Evolution | volume = 6 | issue = 3 | pages = 491–9 | year = 2014 | pmid = 24493383 | doi = 10.1093/gbe/evu023 | url = }}</ref> The duplication that led to RLN1 and RLN2 is thought to have been a result of positive selection and convergent evolution at the nucleotide level between the relaxin gene in New World monkeys and the RLN1 gene in apes .<ref name="Arroyo_2014" /> As a result, Old World monkeys, a group that includes the subfamilies colobines and cercopithecines, have lost the RLN1 paralog, but apes have retained both the RLN1 and the RLN2 genes <ref name="Arroyo_2014" />; Lawrence and Cords, 2012).

==See also==
* [[Relaxin family peptide hormones]]
* [[Insulin/IGF/Relaxin' family]]
* [[Relaxin'/insulin-like family peptide receptor 1]]

== References ==
{{Reflist|2}}

==External links==
* {{MeshName|Relaxin'}}
* {{cite web | url = http://www.hprd.org/resultsQuery?multiplefound=&prot_name=Relaxin&external=Ref_seq&accession_id=&hprd=&gene_symbol=&chromo_locus=&function=&ptm_type=&localization=&domain=&motif=&expression=&prot_start=&prot_end=&limit=0&mole_start=&mole_end=&disease=&query_submit=Search | title = Relaxin | work = Human Protein Reference Database | publisher = Johns Hopkins University and the Institute of Bioinformatics | accessdate = 2009-05-20}}

{{Hormones}}
{{Protein and peptide receptor modulators}}
{{Authority control}}

[[Category:Peptide hormones]]
[[Category:Hormones of the ovary]]
[[Category:Hormones of the placenta]]
[[Category:Hormones of the pregnant female]]
[[Category:Human female endocrine system]]

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Relaxin