Relaxin

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For the Miles Davis album, see Relaxin' with the Miles Davis Quintet.
Relaxin 1
File:Relaxin.png
Identifiers
SymbolRLN1
Alt. symbolsH1
Entrez6013
HUGO10026
OMIM179730
RefSeqNM_006911
UniProtP04808
Other data
LocusChr. 9 qter-q12
Relaxin 2
Identifiers
SymbolRLN2
Alt. symbolsH2, RLXH2, bA12D24.1.1, bA12D24.1.2
Entrez6019
HUGO10027
OMIM179740
PDB6RLX
RefSeqNM_134441
UniProtP04090
Other data
LocusChr. 9 qter-q12
Relaxin 3
Identifiers
SymbolRLN3
Alt. symbolsZINS4, RXN3, H3
Entrez117579
HUGO17135
OMIM606855
RefSeqNM_080864
UniProtQ8WXF3
Other data
LocusChr. 19 p13.3

Relaxin is a protein hormone of about 6000 Da[1] first described in 1926 by Frederick Hisaw.[2][3]

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.[4]

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.[5]

Structure

See also: Insulin/IGF/Relaxin family

Structurally, relaxin is a heterodimer of two peptide chains of 24 and 29 amino acids 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 [1] and nonpregnant[1] 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]). 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.[6] It is believed to soften the pubic symphysis.

In males, relaxin enhances motility of sperm in semen.[7]

In other animals

In animals, relaxin widens the pubic bone and facilitates 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 metalloproteinases.[8] It also enhances angiogenesis and is a potent renal vasodilator.

In the European Rabbit, (Oryctolagus cuniculus), relaxin[9] 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.[10] They contain a heptahelical 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.[11]

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.[12] 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 .[12] 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 [12]; Lawrence and Cords, 2012).

See also

References

  1. ↑ 1.0 1.1 1.2 Bani D (January 1997). "Relaxin: a pleiotropic hormone". General pharmacology. 28 (1): 13–22. doi:10.1016/s0306-3623(96)00171-1. PMID 9112071.
  2. ↑ "If a Gopher Can Do It ..." Time Magazine. 1944-04-10. Retrieved 2009-05-20.
  3. ↑ Becker GJ, Hewitson TD (March 2001). "Relaxin and renal fibrosis". Kidney Int. 59 (3): 1184–5. doi:10.1046/j.1523-1755.2001.0590031184.x. PMID 11231378.
  4. ↑ Wilkinson TN, Speed TP, Tregear GW, Bathgate RA (February 2005). "Evolution of the relaxin-like peptide family". BMC Evolutionary Biology. 5: 14. doi:10.1186/1471-2148-5-14. PMC 551602. PMID 15707501.
  5. ↑ MacLennan AH (1991). "The role of the hormone relaxin in human reproduction and pelvic girdle relaxation". Scandinavian journal of rheumatology. Supplement. 88: 7–15. PMID 2011710.
  6. ↑ Conrad KP (August 2011). "Maternal vasodilation in pregnancy: the emerging role of relaxin". Am. J. Physiol. Regul. Integr. Comp. Physiol. 301 (2): R267–75. doi:10.1152/ajpregu.00156.2011. PMC 3154715. PMID 21613576.
  7. ↑ Weiss G (February 1989). "Relaxin in the male". Biol. Reprod. 40 (2): 197–200. doi:10.1095/biolreprod40.2.197. PMID 2497805.
  8. ↑ Mookerjee I, Solly NR, Royce SG, Tregear GW, Samuel CS, Tang ML (2006). "Endogenous relaxin regulates collagen deposition in an animal model of allergic airway disease". Endocrinology. 147 (2): 754–61. doi:10.1210/en.2005-1006. PMID 16254028.
  9. ↑ Arroyo JI, Hoffmann FG, Opazo JC (2012). "Gene duplication and positive selection explains unusual physiological roles of the relaxin gene in the European rabbit". Journal of Molecular Evolution. 74 (1–2): 52–60. doi:10.1007/s00239-012-9487-2. PMID 22354201.
  10. ↑ Hsu SY, Nakabayashi K, Nishi S, Kumagai J, Kudo M, Sherwood OD, Hsueh AJ (2002). "Activation of orphan receptors by the hormone relaxin". Science. 295 (5555): 674–6. doi:10.1126/science.1065654. PMID 11809971.
  11. ↑ Van Der Westhuizen ET, Summers RJ, Halls ML, Bathgate RA, Sexton PM (2007). "Relaxin receptors--new drug targets for multiple disease states". Curr Drug Targets. 8 (1): 91–104. doi:10.2174/138945007779315650. PMID 17266534.
  12. ↑ 12.0 12.1 12.2 Arroyo JI, Hoffmann FG, Opazo JC (2014). "Evolution of the relaxin/insulin-like gene family in anthropoid primates". Genome Biology and Evolution. 6 (3): 491–9. doi:10.1093/gbe/evu023. PMID 24493383.

External links

  • Relaxin' at the US National Library of Medicine Medical Subject Headings (MeSH)
  • "Relaxin". Human Protein Reference Database. Johns Hopkins University and the Institute of Bioinformatics. Retrieved 2009-05-20.

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