Alternative titles; symbols
HGNC Approved Gene Symbol: RLN1
Cytogenetic location: 9p24.1 Genomic coordinates (GRCh38) : 9:5,334,930-5,340,916 (from NCBI)
Relaxin is a peptide hormone produced by the corpora lutea of ovaries during pregnancy in many mammalian species, including man. The secretion of the hormone into the blood stream just before parturition results in a marked softening and lengthening of the pubic symphysis and a softening of the cervix, which facilitates the birth process. By inhibiting uterine contractions, relaxin may influence the timing of parturition. Like insulin, relaxin consists of 2 peptide chains, A and B, covalently linked by disulfide bonds. By further analogy to insulin, the 2 peptides are synthesized as a single-chain precursor polypeptide with the B chain at the NH2-terminus (summary by Hudson et al., 1984).
Hudson et al. (1981) sequenced the rat relaxin gene. Later, Hudson et al. (1983) determined the structure of the entire coding region of a human preprorelaxin gene and synthesized biologically active relaxin with the structure predicted from that of the genomic clone. Hudson et al. (1984) isolated a second human relaxin gene sequence (RLN2; 179740) from a cDNA clone band prepared from human pregnant ovarian tissue. This (designated H2) appeared to be different from the gene first recovered, called H1, and to be selectively expressed in the ovary during pregnancy. Nucleotide sequence showed striking differences in the predicted structure of relaxin encoded by the 2 genes. There was no evidence of expression of the H1 gene in ovary; whether H1 is expressed in other tissues or is a pseudogene is unclear.
See review by Schwabe and Bullesbach (1994).
By treating cells expressing LGR7 (606654) or LGR8 (606655) with pig relaxin, Hsu et al. (2002) observed a dose-dependent increase in cAMP production. In contrast, treatment with insulin was ineffective. They concluded that LGR7 and LGR8 are receptors for relaxin.
By study of mouse-human cell hybrids, Crawford et al. (1984) found that both relaxin genes are on 9p (9pter-9q12). Only a single relaxin gene is found in the pig, rat and mouse. In the case of the growth hormone genes, 'extra' genes not predicted by known gene products are found in man only. Structural similarities of relaxin to insulin exist at the level of both the gene and the product.
Naggert and Mu (1994) stated that the relaxin gene maps to mouse chromosome 19 near D19Mit23.
Zhao et al. (1999) used gene targeting to generate Rln -/- mice. These mice were fertile but had deficient mammary development such that pups were unable to suckle and died within 24 hrs unless cross-fostered with a wildtype foster mother. Nipple enlargement during pregnancy was slight and histologic analysis demonstrated an appearance of the virgin state, though mammary ducts were grossly dilated and milk was produced. Heterozygous mice lactated normally. Zhao et al. (1999) also noted that the intrapubic ligament failed to relax during pregnancy in Rln -/- mice.
By treating mice with 7BP, the soluble 60-kD extracellular domain of LGR7, from days 17 to 20 after conception, Hsu et al. (2002) blocked parturition for more than a day and caused underdevelopment of nipples, as seen in relaxin null mice. They suggested that analogs of relaxin agonists and antagonists could be useful for the treatment of disorders of labor onset and other conditions affecting organs expressing relaxin receptors.
Crawford, R. J., Hudson, P., Shine, J., Niall, H. D., Eddy, R. L., Shows, T. B. Two human relaxin genes are on chromosome 9. EMBO J. 3: 2341-2345, 1984. [PubMed: 6548703] [Full Text: https://doi.org/10.1002/j.1460-2075.1984.tb02136.x]
Hsu, S. Y., Nakabayashi, K., Nishi, S., Kumagai, J., Kudo, M., Sherwood, O. D., Hsueh, A. J. W. Activation of orphan receptors by the hormone relaxin. Science 295: 671-674, 2002. [PubMed: 11809971] [Full Text: https://doi.org/10.1126/science.1065654]
Hudson, P., Haley, J., Cronk, M., Shine, J., Niall, H. Molecular cloning and characterization of cDNA sequences coding for rat relaxin. Nature 291: 127-131, 1981. [PubMed: 7231533] [Full Text: https://doi.org/10.1038/291127a0]
Hudson, P., Haley, J., John, M., Cronk, M., Crawford, R., Haralambidis, J., Tregear, G., Shine, J., Niall, H. Structure of a genomic clone encoding biologically active human relaxin. Nature 301: 628-831, 1983. [PubMed: 6298628] [Full Text: https://doi.org/10.1038/301628a0]
Hudson, P., John, M., Crawford, R., Haralambidis, J., Scanlon, D., Gorman, J., Tregear, G., Shine, J., Niall, H. Relaxin gene expression in human ovaries and the predicted structure of a human preprorelaxin by analysis of cDNA clones. EMBO J. 3: 2333-2339, 1984. [PubMed: 6548702] [Full Text: https://doi.org/10.1002/j.1460-2075.1984.tb02135.x]
Naggert, J. K., Mu, J.-L. The mouse very low density lipoprotein receptor (Vldlr) gene maps to chromosome 19. Mammalian Genome 5: 453-455, 1994. [PubMed: 7919660] [Full Text: https://doi.org/10.1007/BF00357008]
Schwabe, C., Bullesbach, E. E. Relaxin: structures, functions, promises, and nonevolution. FASEB J. 8: 1152-1160, 1994. [PubMed: 7958621] [Full Text: https://doi.org/10.1096/fasebj.8.14.7958621]
Zhao, L., Roche, P. J., Gunnerson, J. M., Hammond, V. E., Tregear, G. W., Wintour, E. M., Beck, F. Mice without a functional relaxin gene are unable to deliver milk to their pups. Endocrinology 140: 445-453, 1999. [PubMed: 9886856] [Full Text: https://doi.org/10.1210/endo.140.1.6404]