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Gene Review

RLN1  -  relaxin 1

Homo sapiens

Synonyms: H1, H1RLX, RLXH1, bA12D24.3.1, bA12D24.3.2
 
 
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Disease relevance of RLN1

 

Psychiatry related information on RLN1

  • A time study over 13 days of culture showed that the promoter activity increased exponentially to > 10(4) fold in cells treated with medroxyprogesterone acetate (MPA) and relaxin (RLX) [5].
 

High impact information on RLN1

  • Clearly some like relaxin and inhibin function as important hormones, and ABP, for example, probably functions importantly in transporting testosterone down the tubule [6].
  • Relaxin is a peptide hormone synthesized in the corpora lutea of ovaries during pregnancy and is released into the blood stream prior to parturition [7].
  • However, the limited availability of human ovaries during pregnancy has prevented both direct amino acid sequence determination and isolation of cDNA clones obtained from relaxin producing tissue [7].
  • Secretion of ovarian relaxin correlates with secretion of ovarian progesterone, thus providing another index of luteal function [8].
  • All late H1 genes also contain a highly conserved GC-rich sequence resembling a low-affinity binding site for the mammalian transcription factor Sp1 that is required for basal expression of the H1-beta gene at all stages of embryogenesis [9].
 

Chemical compound and disease context of RLN1

 

Biological context of RLN1

  • Relaxin gene expression in human ovaries and the predicted structure of a human preprorelaxin by analysis of cDNA clones [15].
  • Nucleotide sequence analysis revealed striking differences in the predicted structures of relaxin encoded by these two genes [15].
  • We now have evidence that the human genome possesses an additional relaxin-related gene (designated human relaxin gene H2) which appears to be selectively expressed in the ovary during pregnancy [15].
  • In earlier studies we identified in a human genomic library a gene (human relaxin gene H1) coding for a relaxin-related peptide [15].
  • There was no evidence for the expression of human relaxin gene H1 in the ovary and so far it is unclear whether gene H1 is expressed in another tissue or whether it represents a pseudogene [15].
 

Anatomical context of RLN1

 

Associations of RLN1 with chemical compounds

  • The NMR Solution Structure of the Relaxin (RXFP1) Receptor Lipoprotein Receptor Class A Module and Identification of Key Residues in the N-terminal Region of the Module That Mediate Receptor Activation [19].
  • We have confirmed that the corpus luteum does not contain detectable H1 relaxin mRNA [17].
  • The stability of relaxin H1 and H2 mRNAs were compared in LNCaP cells treated with the transcription inhibitor actinomycin D (10 mM) for 0, 1, 2, 4, 8, 10, 14, or 24 h [20].
  • Deletion constructs containing portions of the 5'-flanking regions of H1 and H2 linked to the bacterial chloramphenicol acetyl transferase reporter gene were prepared [2].
  • Thus, both progesterone and glucocorticoids are capable of differentially regulating the expression of the two human relaxin genes in a model system [10].
 

Physical interactions of RLN1

 

Regulatory relationships of RLN1

  • Chemical synthesis of biologically active relaxin based on the sequence obtained from ovarian cDNA clones confirmed that the expressed gene (H2) encodes an authentic human relaxin [15].
  • To this end, we examined the effect of stimulation of RXFP1 and RXFP2 receptors [expressed in human embryonic kidney (HEK) 293T cells] with human relaxin family peptides on a number of transcription factor-response elements coupled to reporter genes [25].
  • The above results indicate that high local uterine RLX concentrations may be involved in uterine quiescence during human pregnancy by down regulating the OTR [26].
  • Relaxin-3 was found to bind to and activate native relaxin receptors in vitro and stimulate water drinking through central relaxin receptors in vivo [27].
  • Relaxin stimulates leukocyte adhesion and migration through a relaxin receptor LGR7-dependent mechanism [28].
 

Other interactions of RLN1

  • Here, we report the solution structure of human relaxin-3, the first structure of a relaxin family member to be solved by NMR methods [29].
  • Our review summarizes our current knowledge of the expression of relaxin and INSL3 in human neoplastic tissues and discusses the etiological roles of these heterodimeric peptide hormones in cancer [30].
  • Comparison of Signaling Pathways Activated by the Relaxin Family Peptide Receptors, RXFP1 and RXFP2, Using Reporter Genes [25].
  • The purpose of this study was to evaluate a possible effect of RLX on OTR regulation in human uterine smooth muscle cells [26].
  • The INSL4 gene maps close to WI-5527 at 9p24.1-->p23.3 clustered with two relaxin genes and outside the critical region for the monosomy 9p syndrome [31].
 

Analytical, diagnostic and therapeutic context of RLN1

References

  1. Functional expression of mouse relaxin and mouse relaxin-3 in the lung from an Ebola virus glycoprotein-pseudotyped lentivirus via tracheal delivery. Silvertown, J.D., Walia, J.S., Summerlee, A.J., Medin, J.A. Endocrinology (2006) [Pubmed]
  2. Characterization of human relaxin gene regulation in the relaxin-expressing human prostate adenocarcinoma cell line LNCaP.FGC. Gunnersen, J.M., Roche, P.J., Tregear, G.W., Crawford, R.J. J. Mol. Endocrinol. (1995) [Pubmed]
  3. Human medullary thyroid carcinoma: a source and potential target for relaxin-like hormones. Klonisch, T., Mustafa, T., Bialek, J., Radestock, Y., Holzhausen, H.J., Dralle, H., Hoang-Vu, C., Hombach-Klonisch, S. Ann. N. Y. Acad. Sci. (2005) [Pubmed]
  4. Relaxin receptors--new drug targets for multiple disease states. Van Der Westhuizen, E.T., Summers, R.J., Halls, M.L., Bathgate, R.A., Sexton, P.M. Current drug targets (2007) [Pubmed]
  5. Activation of the human IGFBP-1 gene promoter by progestin and relaxin in primary culture of human endometrial stromal cells. Gao, J.G., Mazella, J., Tseng, L. Mol. Cell. Endocrinol. (1994) [Pubmed]
  6. Nonsteroidal signals originating in the gonads. Ackland, J.F., Schwartz, N.B., Mayo, K.E., Dodson, R.E. Physiol. Rev. (1992) [Pubmed]
  7. Structure of a genomic clone encoding biologically active human relaxin. Hudson, P., Haley, J., John, M., Cronk, M., Crawford, R., Haralambidis, J., Tregear, G., Shine, J., Niall, H. Nature (1983) [Pubmed]
  8. Cellulosic microfibrils: nascent stages of synthesis in a higher plant cell. Weiss, G., O'Byrne, E.M., Steinetz, B.G. Science (1976) [Pubmed]
  9. Both basal and ontogenic promoter elements affect the timing and level of expression of a sea urchin H1 gene during early embryogenesis. Lai, Z.C., Maxson, R., Childs, G. Genes Dev. (1988) [Pubmed]
  10. Regulation of the human relaxin genes H1 and H2 by steroid hormones. Garibay-Tupas, J.L., Okazaki, K.J., Tashima, L.S., Yamamoto, S., Bryant-Greenwood, G.D. Mol. Cell. Endocrinol. (2004) [Pubmed]
  11. Relaxin and relaxin c-peptide levels in human reproductive tissues. MacLennan, A.H., Grant, P., Borthwick, A.C. Reprod. Fertil. Dev. (1991) [Pubmed]
  12. Inotropic responses to human gene 2 (B29) relaxin in a rat model of myocardial infarction (MI): effect of pertussis toxin. Kompa, A.R., Samuel, C.S., Summers, R.J. Br. J. Pharmacol. (2002) [Pubmed]
  13. Single-dose haloperidol for the prophylaxis of postoperative nausea and vomiting after intrathecal morphine. Parlow, J.L., Costache, I., Avery, N., Turner, K. Anesth. Analg. (2004) [Pubmed]
  14. Relaxin induces an extracellular matrix-degrading phenotype in human lung fibroblasts in vitro and inhibits lung fibrosis in a murine model in vivo. Unemori, E.N., Pickford, L.B., Salles, A.L., Piercy, C.E., Grove, B.H., Erikson, M.E., Amento, E.P. J. Clin. Invest. (1996) [Pubmed]
  15. Relaxin gene expression in human ovaries and the predicted structure of a human preprorelaxin by analysis of cDNA clones. Hudson, P., John, M., Crawford, R., Haralambidis, J., Scanlon, D., Gorman, J., Tregear, G., Shine, J., Niall, H. EMBO J. (1984) [Pubmed]
  16. Relaxin enhances the oncogenic potential of human thyroid carcinoma cells. Hombach-Klonisch, S., Bialek, J., Trojanowicz, B., Weber, E., Holzhausen, H.J., Silvertown, J.D., Summerlee, A.J., Dralle, H., Hoang-Vu, C., Klonisch, T. Am. J. Pathol. (2006) [Pubmed]
  17. Expression of the human relaxin H1 gene in the decidua, trophoblast, and prostate. Hansell, D.J., Bryant-Greenwood, G.D., Greenwood, F.C. J. Clin. Endocrinol. Metab. (1991) [Pubmed]
  18. Increased expression of the relaxin receptor (LGR7) in human endometrium during the secretory phase of the menstrual cycle. Bond, C.P., Parry, L.J., Samuel, C.S., Gehring, H.M., Lederman, F.L., Rogers, P.A., Summers, R.J. J. Clin. Endocrinol. Metab. (2004) [Pubmed]
  19. The NMR Solution Structure of the Relaxin (RXFP1) Receptor Lipoprotein Receptor Class A Module and Identification of Key Residues in the N-terminal Region of the Module That Mediate Receptor Activation. Hopkins, E.J., Layfield, S., Ferraro, T., Bathgate, R.A., Gooley, P.R. J. Biol. Chem. (2007) [Pubmed]
  20. Isolation and analysis of the 3'-untranslated regions of the human relaxin H1 and H2 genes. Garibay-Tupas, J.L., Bao, S., Kim, M.T., Tashima, L.S., Bryant-Greenwood, G.D. J. Mol. Endocrinol. (2000) [Pubmed]
  21. The receptor-binding site of human relaxin II. A dual prong-binding mechanism. Büllesbach, E.E., Yang, S., Schwabe, C. J. Biol. Chem. (1992) [Pubmed]
  22. Characteristics of the binding of 32P-labelled human relaxins to the human fetal membranes. Garibay-Tupas, J.L., Maaskant, R.A., Greenwood, F.C., Bryant-Greenwood, G.D. J. Endocrinol. (1995) [Pubmed]
  23. The trap-like relaxin-binding site of the leucine-rich G-protein-coupled receptor 7. Büllesbach, E.E., Schwabe, C. J. Biol. Chem. (2005) [Pubmed]
  24. Ligand activated relaxin receptor increases the transcription of IGFBP-1 and prolactin in human decidual and endometrial stromal cells. Tang, M., Mazella, J., Zhu, H.H., Tseng, L. Mol. Hum. Reprod. (2005) [Pubmed]
  25. Comparison of Signaling Pathways Activated by the Relaxin Family Peptide Receptors, RXFP1 and RXFP2, Using Reporter Genes. Halls, M.L., Bathgate, R.A., Summers, R.J. J. Pharmacol. Exp. Ther. (2007) [Pubmed]
  26. The effect of relaxin on the oxytocin receptor in human uterine smooth muscle cells. Friebe-Hoffmann, U., Baston, D.M., Chiao, J.P., Winebrenner, L.D., Krüssel, J.S., Hoffmann, T.K., Hirchenhain, J., Rauk, P.N. Regul. Pept. (2007) [Pubmed]
  27. The chemistry and biology of human relaxin-3. Tregear, G.W., Bathgate, R.A., Layfield, S., Ferraro, T., Gundlach, A., Ma, S., Lin, F., Hanson, N.F., Summers, R.J., Rosengren, J., Craik, D.J., Wade, J.D. Ann. N. Y. Acad. Sci. (2005) [Pubmed]
  28. Relaxin stimulates leukocyte adhesion and migration through a relaxin receptor LGR7-dependent mechanism. Figueiredo, K.A., Mui, A.L., Nelson, C.C., Cox, M.E. J. Biol. Chem. (2006) [Pubmed]
  29. Solution structure and novel insights into the determinants of the receptor specificity of human relaxin-3. Rosengren, K.J., Lin, F., Bathgate, R.A., Tregear, G.W., Daly, N.L., Wade, J.D., Craik, D.J. J. Biol. Chem. (2006) [Pubmed]
  30. Relaxin-like peptides in cancer. Silvertown, J.D., Summerlee, A.J., Klonisch, T. Int. J. Cancer (2003) [Pubmed]
  31. The INSL4 gene maps close to WI-5527 at 9p24.1-->p23.3 clustered with two relaxin genes and outside the critical region for the monosomy 9p syndrome. Veitia, R., Laurent, A., Quintana-Murci, L., Ottolenghi, C., Fellous, M., Vidaud, M., McElreavey, K. Cytogenet. Cell Genet. (1998) [Pubmed]
  32. Relaxin gene expression in human reproductive tissues by in situ hybridization. Bogic, L.V., Mandel, M., Bryant-Greenwood, G.D. J. Clin. Endocrinol. Metab. (1995) [Pubmed]
  33. Physiological or pathological--a role for relaxin in the cardiovascular system? Samuel, C.S., Parry, L.J., Summers, R.J. Current opinion in pharmacology. (2003) [Pubmed]
 
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