Relaxin signaling in reproductive tissues.
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.
Hsu
Sheau Yu Teddy
SY
Division of Reproductive Biology, Department of Gynecology and Obstetrics, Stanford University School of Medicine, Stanford, CA 94305-5317, USA. teddyhsu@stanford.edu
Nakabayashi
Koji
K
Nishi
Shinya
S
Kumagai
Jin
J
Kudo
Masataka
M
Bathgate
Ross A D
RA
Sherwood
O David
OD
Hsueh
Aaron J W
AJ
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
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