Relaxin

Relaxin 1
Identifiers
Symbol RLN1
Alt. symbols H1
Entrez 6013
HUGO 10026
OMIM 179730
RefSeq NM_006911
UniProt P04808
Other data
Locus Chr. 9 qter-q12
Relaxin 2
Identifiers
Symbol RLN2
Alt. symbols H2, RLXH2, bA12D24.1.1, bA12D24.1.2
Entrez 6019
HUGO 10027
OMIM 179740
PDB 6RLX
RefSeq NM_134441
UniProt P04090
Other data
Locus Chr. 9 qter-q12
Relaxin 3
Identifiers
Symbol RLN3
Alt. symbols ZINS4, RXN3, H3
Entrez 117579
HUGO 17135
OMIM 606855
RefSeq NM_080864
UniProt Q8WXF3
Other data
Locus Chr. 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

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.

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 ). 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.

Receptors

Relaxin interacts with the relaxin receptor LGR7 (RXFP1) and LGR8 (RXFP2), which belong to the G protein-coupled receptor superfamily.[9] 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.[10]

Pharmacological targets

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

See also

References

  1. 1 2 3 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 551602Freely accessible. 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 3154715Freely accessible. 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. ↑ 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.
  10. ↑ 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.
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