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Gene Review

Rln1  -  relaxin 1

Rattus norvegicus

Synonyms: Prorelaxin 1, Rln
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Disease relevance of Rln1

  • Relaxin has antifibrotic effects on the hepatic stellate cells (HSCs) responsible for collagen deposition in cirrhosis [1].
  • The expression of relaxin receptors LGR7 and LGR8 in HSCs and liver disease was examined [1].
  • Relaxin (100 ng) was given intravenously 30 minutes before ischemia [2].
  • Relaxin inhibits effective collagen deposition by cultured hepatic stellate cells and decreases rat liver fibrosis in vivo [3].
  • These data indicate that relaxin-induced uterine edema and growth is mediated by ERs [4].

Psychiatry related information on Rln1

  • A second set of experiments was done to examine the effects of neutralizing the central actions of relaxin on drinking behavior in pregnancy [5].

High impact information on Rln1


Chemical compound and disease context of Rln1

  • Following treatment with 17beta-estradiol or relaxin alone, the uterine weight/body weight ratio (UtW/BW) increased significantly over control values (+98% and +77% respectively, p<0.0003) [4].
  • Pretreatment of cells with pertussis toxin or replacement of extracellular calcium with 2 mM EGTA inhibited the oxytocin-induced increase in intracellular calcium by 47% and 50%, respectively, but did not inhibit the action of relaxin [8].
  • 6. Relaxin was much less potent against the spasm dependent upon intracellular Ca2+ (that induced by oxytocin (20 nM) + nifedipine (500 nM)) than against the spasms dependent upon extracellular Ca2+, those induced by oxytocin (0.2 nM) and Bay K 8644 (1 microM) [9].
  • The depression in collagen concentration and increase in apparent rate of proline incorporation into collagen induced by relaxin alone were also eliminated, indicating a fundamental blockade of the effect of relaxin in this experimental design as well as a close association of changes in collagen concentration with tissue hypertrophy [10].
  • Effect of relaxin on myocardial ischemia injury induced by isoproterenol [11].

Biological context of Rln1

  • The nucleotide sequence of these clones demonstrates that relaxin is synthesized as a preprorelaxin molecule with an unexpectedly large connecting peptide of 105 amino acid residues [12].
  • Comparison with porcine relaxin reveals a clear sequence homology but the extent of this is much more limited than expected, with only 21 of 53 residues (39.6%) in corresponding positions being identical [13].
  • We have isolated rat relaxin as a single chromatographic component and determined its complete amino acid sequence [13].
  • The major objectives of the present work were to determine whether relaxin administration to nonpregnant rats 1) modifies cardiac output (CO), systemic vascular resistance, and global arterial compliance (AC), and 2) regulates the passive mechanics of isolated arteries [14].
  • Localization of LGR7 (relaxin receptor) mRNA and protein in rat forebrain: correlation with relaxin binding site distribution [15].

Anatomical context of Rln1


Associations of Rln1 with chemical compounds

  • It is likely that circulating relaxin also stimulates neurons in the OVLT that influence vasopressin secretion [17].
  • A novel, adenylate cyclase, signaling mechanism of relaxin H2 action [18].
  • They also raise the likelihood of a role for relaxin in other cardiovascular changes of pregnancy, and they suggest that, like estrogen, relaxin should be considered a regulator of cardiovascular function [19].
  • In contrast, the renal vasoconstrictory response to angiotensin II was attenuated by the RLX treatment [20].
  • It is suggested that relaxin may have a physiological role in modulating mast cell function through the L-arginine-nitric oxide pathway [21].

Regulatory relationships of Rln1


Other interactions of Rln1

  • Relaxin 3/INSL 7 has recently been identified as a new member of the insulin/relaxin superfamily [16].
  • Discrete neuronal populations in brain express relaxin and relaxin-3, and molecular studies have identified former-orphan, G-protein-coupled receptors LGR7 and GPCR135 as their native receptors [15].
  • Relaxin administration resulted in increased Fos expression in the subfornical organ (SFO), organum vasculosum of the lamina terminalis (OVLT), median preoptic nucleus, and magnocellular neurons in the supraoptic and paraventricular nuclei [17].
  • The reproductive hormone relaxin has been reported to reduce collagen and TIMP-1 expression by dermal and lung fibroblasts and thus has potential antifibrotic activity in liver fibrosis [3].
  • To gain insight into the role of ERbeta in estrogen action, we examined the effects of estrogen and relaxin, a ligand-independent activator of ERs, on the expression of ERbeta1 and ERbeta2 mRNA in the uterus in vivo [23].

Analytical, diagnostic and therapeutic context of Rln1


  1. Relaxin receptor expression in hepatic stellate cells and in cirrhotic rat liver tissue. Bennett, R.G., Mahan, K.J., Gentry-Nielsen, M.J., Tuma, D.J. Ann. N. Y. Acad. Sci. (2005) [Pubmed]
  2. Relaxin protects against myocardial injury caused by ischemia and reperfusion in rat heart. Bani, D., Masini, E., Bello, M.G., Bigazzi, M., Sacchi, T.B. Am. J. Pathol. (1998) [Pubmed]
  3. Relaxin inhibits effective collagen deposition by cultured hepatic stellate cells and decreases rat liver fibrosis in vivo. Williams, E.J., Benyon, R.C., Trim, N., Hadwin, R., Grove, B.H., Arthur, M.J., Unemori, E.N., Iredale, J.P. Gut (2001) [Pubmed]
  4. Relaxin stimulates uterine edema via activation of estrogen receptors: blockade of its effects using ICI 182,780, a specific estrogen receptor antagonist. Pillai, S.B., Rockwell, L.C., Sherwood, O.D., Koos, R.D. Endocrinology (1999) [Pubmed]
  5. The dipsogenic effects of rat relaxin: The effect of photoperiod and the potential role of relaxin on drinking in pregnancy. Summerlee, A.J., Hornsby, D.J., Ramsey, D.G. Endocrinology (1998) [Pubmed]
  6. Relaxin affects the release of oxytocin and vasopressin from the neurohypophysis. Dayanithi, G., Cazalis, M., Nordmann, J.J. Nature (1987) [Pubmed]
  7. Relaxin affects the central control of oxytocin release. Summerlee, A.J., O'Byrne, K.T., Paisley, A.C., Breeze, M.F., Porter, D.G. Nature (1984) [Pubmed]
  8. Antagonism of contractants and relaxants at the level of intracellular calcium and phosphoinositide turnover in the rat uterus. Anwer, K., Hovington, J.A., Sanborn, B.M. Endocrinology (1989) [Pubmed]
  9. Cellular localization of the inhibitory action of relaxin against uterine spasm. Hughes, S.J., Hollingsworth, M. Br. J. Pharmacol. (1995) [Pubmed]
  10. Progesterone inhibits the uterotrophic effect of relaxin in immature rats. Adams, W.C., Hanousek, C.A., Frieden, E.H. Proc. Soc. Exp. Biol. Med. (1989) [Pubmed]
  11. Effect of relaxin on myocardial ischemia injury induced by isoproterenol. Zhang, J., Qi, Y.F., Geng, B., Pan, C.S., Zhao, J., Chen, L., Yang, J., Chang, J.K., Tang, C.S. Peptides (2005) [Pubmed]
  12. Molecular cloning and characterization of cDNA sequences coding for rat relaxin. Hudson, P., Haley, J., Cronk, M., Shine, J., Niall, H. Nature (1981) [Pubmed]
  13. Limited sequence homology between porcine and rat relaxins: implications for physiological studies. John, M.J., Borjesson, B.W., Walsh, J.R., Niall, H.D. Endocrinology (1981) [Pubmed]
  14. Relaxin modifies systemic arterial resistance and compliance in conscious, nonpregnant rats. Conrad, K.P., Debrah, D.O., Novak, J., Danielson, L.A., Shroff, S.G. Endocrinology (2004) [Pubmed]
  15. Localization of LGR7 (relaxin receptor) mRNA and protein in rat forebrain: correlation with relaxin binding site distribution. Burazin, T.C., Johnson, K.J., Ma, S., Bathgate, R.A., Tregear, G.W., Gundlach, A.L. Ann. N. Y. Acad. Sci. (2005) [Pubmed]
  16. Neurons expressing relaxin 3/INSL 7 in the nucleus incertus respond to stress. Tanaka, M., Iijima, N., Miyamoto, Y., Fukusumi, S., Itoh, Y., Ozawa, H., Ibata, Y. Eur. J. Neurosci. (2005) [Pubmed]
  17. Circulating relaxin acts on subfornical organ neurons to stimulate water drinking in the rat. Sunn, N., Egli, M., Burazin, T.C., Burns, P., Colvill, L., Davern, P., Denton, D.A., Oldfield, B.J., Weisinger, R.S., Rauch, M., Schmid, H.A., McKinley, M.J. Proc. Natl. Acad. Sci. U.S.A. (2002) [Pubmed]
  18. A novel, adenylate cyclase, signaling mechanism of relaxin H2 action. Shpakov, A., Pertseva, M., Kuznetsova, L., Plesneva, S. Ann. N. Y. Acad. Sci. (2005) [Pubmed]
  19. Relaxin is essential for renal vasodilation during pregnancy in conscious rats. Novak, J., Danielson, L.A., Kerchner, L.J., Sherwood, O.D., Ramirez, R.J., Moalli, P.A., Conrad, K.P. J. Clin. Invest. (2001) [Pubmed]
  20. Relaxin is a potent renal vasodilator in conscious rats. Danielson, L.A., Sherwood, O.D., Conrad, K.P. J. Clin. Invest. (1999) [Pubmed]
  21. 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]
  22. Induction of relaxin messenger RNA expression in response to prolactin receptor activation requires protein kinase C delta signaling. Peters, C.A., Maizels, E.T., Robertson, M.C., Shiu, R.P., Soloff, M.S., Hunzicker-Dunn, M. Mol. Endocrinol. (2000) [Pubmed]
  23. Treatment of rats with 17beta-estradiol or relaxin rapidly inhibits uterine estrogen receptor beta1 and beta2 messenger ribonucleic acid levels. Pillai, S.B., Jones, J.M., Koos, R.D. Biol. Reprod. (2002) [Pubmed]
  24. Relaxin stimulates plasminogen activator secretion by rat granulosa cells in vitro. Too, C.K., Weiss, T.J., Bryant-Greenwood, G.D. Endocrinology (1982) [Pubmed]
  25. Autoradiographic localization of relaxin binding sites in rat brain. Osheroff, P.L., Phillips, H.S. Proc. Natl. Acad. Sci. U.S.A. (1991) [Pubmed]
  26. Relaxin binding in the rat heart atrium. Osheroff, P.L., Cronin, M.J., Lofgren, J.A. Proc. Natl. Acad. Sci. U.S.A. (1992) [Pubmed]
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