title: Relaxin signaling in reproductive tissues.
abstract: The insulin/relaxin peptide family includes insulin, IGFs, relaxin1-3, INSL3/RLF, INSL4, INSL5/RIF2 and INSL6/RIF1, many without functional characterization. Based on analysis of transgenic phenotypes and phylogenetic profiling, we have discovered that two orphan leucine-rich repeat-containing G protein-coupled receptors, LGR7 and LGR8, are cognate receptors for relaxin whereas INSL3 is a specific ligand for LGR8. With the identification of the relaxin receptors, it is now possible to investigate specific cells and tissues that are responsive to relaxin in diverse physiological and pathological conditions as well as to develop agonists and antagonists for LGR7 and LGR8 as therapeutics to treat different labor disorders. Furthermore, future functional characterization of the specificity of these pluripoentent receptors with peptide ligands could lead to the understanding of related orphan ligands and receptors.
authors.affiliation: Division of Reproductive Biology, Department of Gynecology and Obstetrics, Stanford University School of Medicine, Stanford, CA 94305-5317, USA. teddyhsu@stanford.edu
authors.forename: Sheau Yu Teddy
authors.initials: SY
authors.lastname: Hsu
authors.forename: Koji
authors.initials: K
authors.lastname: Nakabayashi
authors.forename: Shinya
authors.initials: S
authors.lastname: Nishi
authors.forename: Jin
authors.initials: J
authors.lastname: Kumagai
authors.forename: Masataka
authors.initials: M
authors.lastname: Kudo
authors.forename: Ross A D
authors.initials: RA
authors.lastname: Bathgate
authors.forename: O David
authors.initials: OD
authors.lastname: Sherwood
authors.forename: Aaron J W
authors.initials: AJ
authors.lastname: Hsueh
mesh_terms: D000818:Animals; D001483:Base Sequence; D002460:Cell Line; D018076:DNA, Complementary / Q000235:genetics; D005260:Female; D006801:Humans; D007328:Insulin; D008024:Ligands; D008297:Male; D008565:Membrane Proteins / Q000235:genetics / Q000502:physiology; D051379:Mice; D010053:Ovary / Q000502:physiology; D011247:Pregnancy; D011506:Proteins / Q000235:genetics / Q000502:physiology; D043562:Receptors, G-Protein-Coupled / Q000235:genetics / Q000502:physiology; D018000:Receptors, Peptide / Q000235:genetics / Q000502:physiology; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D012065:Relaxin / Q000235:genetics / Q000502:physiology*; D012098:Reproduction / Q000502:physiology*; D015398:Signal Transduction; D013737:Testis / Q000502:physiology; D014018:Tissue Distribution
chemical_list: D018076:DNA, Complementary; D007328:Insulin; C084797:Leydig insulin-like protein; D008024:Ligands; D008565:Membrane Proteins; D011506:Proteins; C417543:RXFP1 protein, human; D043562:Receptors, G-Protein-Coupled; D018000:Receptors, Peptide; D011994:Recombinant Proteins; C033395:relaxin receptors; D012065:Relaxin