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Gene Review

RLN  -  relaxin

Sus scrofa

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Disease relevance of RLN

  • Transformation of E. coli with this plasmid followed by suitable induction resulted in the synthesis of a new protein identified as prorelaxin by its size and its antigenic similarity to relaxin [1].
  • The current study provides first experimental evidence that relaxin has a powerful protective effect on the heart undergoing ischemia and reperfusion acting through a nitric oxide-driven mechanism [2].
  • In the presence of porcine relaxin antiserum and complement, a zone of hemolysis, a plaque, developed around relaxin-releasing LLCs [3].
  • Moreover, in lactating sows (n = 9), 6-10 days post partum, the administration of porcine relaxin (1.5 or 3.0 mg) intravenously, immediately before a suckling episode, did not affect the plasma oxytocin profile compared with saline treatments (within sow) nor did it alter suckling behaviour or the weight gain of the litter [4].
  • We conclude that two i.m. injections of relaxin facilitated earlier calving, acutely decreased progesterone secretion, increased cervical dilatation and pelvic area expansion, and decreased the incidence of dystocia in dairy heifers [5].

Psychiatry related information on RLN

  • Observations that uterotrophic effects of relaxin (RLX) in neonatal gilts were inhibited by the antiestrogen ICI 182,780 suggested that a RLX signaling system, capable of cross-talk with the estrogen receptor, evolves during a critical period for uterine programming (PND 0-14) [6].
  • A decrease (P < 0.05) in circulating relaxin was observed before and immediately after copulation [7].

High impact information on RLN

  • Therefore, we tested whether the administration of RLX elicits renal vasodilation and hyperfiltration in conscious adult, intact female rats [8].
  • Short-term infusion of purified porcine RLX to conscious rats over several hours failed to increase ERPF and GFR [8].
  • The nitric oxide synthase inhibitor Nomega-nitro-L-arginine methyl ester completely abrogated the increase in ERPF and GFR elicited by chronic administration of purified porcine RLX [8].
  • The experiments with drugs capable of influencing nitric oxide production also provide indirect evidence that the inhibiting effect of relaxin on mast cell histamine release is related to an increased generation of nitric oxide [9].
  • The results of the current study demonstrate that relaxin inhibits histamine release by mast cells [9].

Chemical compound and disease context of RLN

  • These studies suggest a non-gonadal source of boar relaxin that is not correlated with testicular growth or testosterone concentrations, is modulated by copulation and by hCG but only at specific stages of development [7].
  • This finding helps explain the two paradoxical roles of relaxin: it inhibits spontaneous myometrial contractility during pregnancy and thus preterm labor but is able to facilitate labor at term through its cervical ripening action without inhibiting the oxytocin- and prostaglandin-driven contractions of parturition [10].

Biological context of RLN

  • Abundant (A)n.(T)n mononucleotide repeats in the pig genome: linkage mapping of the porcine APOB, FSA, ALOX12, PEPN and RLN loci [11].
  • The sequence derived from these cosmids was used to characterize the relaxin gene transcription unit utilized in the pregnant ovary [12].
  • Analysis of chromosomal and cosmid DNA has shown that porcine relaxin is encoded by a single copy gene, comprising two exons separated by a 5.5-kilobase intron [12].
  • Relaxin is an important regulator of uterine function during pregnancy acting systemically to suppress myometrial activity and promote cervical dilation at parturition [13].
  • Although the major source of relaxin in pigs is the corpus luteum of pregnancy, there is now evidence for relaxin gene expression and translation into protein in the theca interna cells of the preovulatory follicle, the corpus luteum of the cycle and the uterus [13].

Anatomical context of RLN

  • Relaxin is a peptide hormone produced by the corpora lutea of ovaries during pregnancy, softening and lengthening the ligaments of the pelvis and softening the cervix in order to make childbirth easier [14].
  • The theca interna cells retain their ability to express the relaxin gene and protein following ovulation [13].
  • The changes in thecal relaxin production during follicle development and its ability to promote growth and changes in proteolytic enzyme activity of granulosa cells in vitro have led to the concept of an autocrine or paracrine role for relaxin within the follicle [13].
  • Relaxin has been identified in boar seminal plasma and can maintain or increase sperm motility [13].
  • Uterotrophic effects of relaxin have been reported in rodents and swine and support the hypothesis that relaxin promotes uterine growth and expansion in early pregnancy to accommodate the growing fetuses [13].

Associations of RLN with chemical compounds

  • During the early stages of development of the corpus luteum, the theca-derived small lutein cells are the source of the relaxin transcript [13].
  • As the corpus luteum becomes fully functional, there is a switch in the site of relaxin synthesis from small theca-derived lutein cells to large granulosa-derived cells [13].
  • However, RLX increased both uterine weight and luminal epithelial height by PND 14 (P < .05), after overt endometrial ER expression [15].
  • The genome of the tunicate Ciona intestinalis contains a relaxin coding region that is organized like a mammalian gene, i.e., signal peptide, B-chain domain, connecting peptide domain, followed by the A-chain domain with a stop codon after cysteine A-22 [16].
  • The role of relaxin in mammary development was studied between days 80-110 of pregnancy in ovariectomized gilts given progesterone to maintain pregnancy [17].

Physical interactions of RLN


Regulatory relationships of RLN


Other interactions of RLN


Analytical, diagnostic and therapeutic context of RLN


  1. Cloning and expression of a porcine prorelaxin gene in E. coli. Stewart, A.G., Richards, H., Roberts, S., Warwick, J., Edwards, K., Bell, L., Smith, J., Derbyshire, R. Nucleic Acids Res. (1983) [Pubmed]
  2. Relaxin counteracts myocardial damage induced by ischemia-reperfusion in isolated guinea pig hearts: evidence for an involvement of nitric oxide. Masini, E., Bani, D., Bello, M.G., Bigazzi, M., Mannaioni, P.F., Sacchi, T.B. Endocrinology (1997) [Pubmed]
  3. Effect of antimicrotubule agents on secretion of relaxin by large luteal cells derived from pregnant swine. Taylor, M.J., Clark, C.L. Endocrinology (1990) [Pubmed]
  4. Lack of effect of relaxin on oxytocin output from the porcine neural lobe in vitro or in lactating sows in vivo. Porter, D.G., Ryan, P.L., Norman, L. J. Reprod. Fertil. (1992) [Pubmed]
  5. Effect of relaxin on facilitation of parturition in dairy heifers. Bagna, B., Schwabe, C., Anderson, L.L. J. Reprod. Fertil. (1991) [Pubmed]
  6. Expression of LGR7 and LGR8 by neonatal porcine uterine tissues and transmission of milk-borne relaxin into the neonatal circulation by suckling. Yan, W., Wiley, A.A., Bathgate, R.A., Frankshun, A.L., Lasano, S., Crean, B.D., Steinetz, B.G., Bagnell, C.A., Bartol, F.F. Endocrinology (2006) [Pubmed]
  7. Relaxin in peripheral plasma of boars during development, copulation, after administration of hCG and after castration. Juang, H.H., Musah, A.I., Schwabe, C., Ford, J.J., Anderson, L.L. J. Reprod. Fertil. (1996) [Pubmed]
  8. Relaxin is a potent renal vasodilator in conscious rats. Danielson, L.A., Sherwood, O.D., Conrad, K.P. J. Clin. Invest. (1999) [Pubmed]
  9. Effects of relaxin on mast cells. In vitro and in vivo studies in rats and guinea pigs. Masini, E., Bani, D., Bigazzi, M., Mannaioni, P.F., Bani-Sacchi, T. J. Clin. Invest. (1994) [Pubmed]
  10. Effect of porcine relaxin on spontaneous, oxytocin-driven and prostaglandin-driven pig myometrial activity in vitro. Pupula, M., MacLennan, A.H. The Journal of reproductive medicine. (1989) [Pubmed]
  11. Abundant (A)n.(T)n mononucleotide repeats in the pig genome: linkage mapping of the porcine APOB, FSA, ALOX12, PEPN and RLN loci. Ellegren, H. Anim. Genet. (1993) [Pubmed]
  12. Porcine relaxin. Gene structure and expression. Haley, J., Crawford, R., Hudson, P., Scanlon, D., Tregear, G., Shine, J., Niall, H. J. Biol. Chem. (1987) [Pubmed]
  13. Sources and biological actions of relaxin in pigs. Bagnell, C.A., Zhang, Q., Downey, B., Ainsworth, L. J. Reprod. Fertil. Suppl. (1993) [Pubmed]
  14. Porcine relaxin: molecular cloning and cDNA structure. Haley, J., Hudson, P., Scanlon, D., John, M., Cronk, M., Shine, J., Tregear, G., Niall, H. DNA (1982) [Pubmed]
  15. Effects of relaxin on neonatal porcine uterine growth and development. Bagnell, C.A., Yan, W., Wiley, A.A., Bartol, F.F. Ann. N. Y. Acad. Sci. (2005) [Pubmed]
  16. Porcine relaxin, a 500 million-year-old hormone? the tunicate Ciona intestinalis has porcine relaxin. Georges, D., Schwabe, C. FASEB J. (1999) [Pubmed]
  17. Effect of relaxin on mammary development in ovariectomized pregnant gilts. Hurley, W.L., Doane, R.M., O'Day-Bowman, M.B., Winn, R.J., Mojonnier, L.E., Sherwood, O.D. Endocrinology (1991) [Pubmed]
  18. Transforming growth factor-beta is a potent inhibitor of basal and stimulated relaxin release by porcine luteal cells maintained in monolayer culture. Taylor, M.J., Clark, C.L. J. Endocrinol. (1992) [Pubmed]
  19. Relaxin increases secretion of tissue inhibitor of matrix metalloproteinase-1 and -2 during uterine and cervical growth and remodeling in the pig. Lenhart, J.A., Ryan, P.L., Ohleth, K.M., Palmer, S.S., Bagnell, C.A. Endocrinology (2002) [Pubmed]
  20. Stimulatory effect of phorbol diester on relaxin release by porcine luteal cells in culture. Taylor, M.J., Clark, C.L. Biol. Reprod. (1988) [Pubmed]
  21. Synergistic effects of insulin-like growth factor I and gonadotrophins on relaxin and progesterone secretion by ageing corpora lutea of pigs. Huang, C.J., Li, Y., Stromer, M.H., Anderson, L.L. J. Reprod. Fertil. (1992) [Pubmed]
  22. Relaxin increases insulin-like growth factors (IGFs) and IGF-binding proteins of the pig uterus in vivo. Ohleth, K.M., Lenhart, J.A., Ryan, P.L., Radecki, S.V., Bagnell, C.A. Endocrinology (1997) [Pubmed]
  23. Relaxin and progesterone secretion as affected by luteinizing hormone and prolactin after hysterectomy in the pig. Felder, K.J., Klindt, J., Bolt, D.J., Anderson, L.L. Endocrinology (1988) [Pubmed]
  24. Relaxin stimulation of porcine granulosa cell deoxyribonucleic acid synthesis in vitro: interactions with insulin and insulin-like growth factor I. Zhang, Q., Bagnell, C.A. Endocrinology (1993) [Pubmed]
  25. Ripening of the human cervix and induction of labour with purified porcine relaxin. MacLennan, A.H., Green, R.C., Bryant-Greenwood, G.D., Greenwood, F.C., Seamark, R.F. Lancet (1980) [Pubmed]
  26. Regulation of relaxin release from monodispersed porcine luteal cells: effect of calcium ionophore A23187 and calcium channel blockers. Taylor, M.J., Clark, C.L. Endocrinology (1988) [Pubmed]
  27. Development of a homologous radioimmunoassay for rat relaxin. Sherwood, O.D., Crnekovic, V.E. Endocrinology (1979) [Pubmed]
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