Activation of orphan receptors by the hormone relaxin.
Relaxin is a hormone important for the growth and remodeling of reproductive and other tissues during pregnancy. Although binding sites for relaxin are widely distributed, the nature of its receptor has been elusive. Here, we demonstrate that two orphan heterotrimeric guanine nucleotide binding protein (G protein)-coupled receptors, LGR7 and LGR8, are capable of mediating the action of relaxin through an adenosine 3',5'-monophosphate (cAMP)-dependent pathway distinct from that of the structurally related insulin and insulin-like growth factor family ligand. Treatment of antepartum mice with the soluble ligand-binding region of LGR7 caused parturition delay. The wide and divergent distribution of the two relaxin receptors implicates their roles in reproductive, brain, renal, cardiovascular, and other functions.
Hsu
Sheau Yu
SY
Division of Reproductive Biology, Department of Gynecology and Obstetrics, Stanford University School of Medicine, Stanford, CA 94305, USA.
Nakabayashi
Koji
K
Nishi
Shinya
S
Kumagai
Jin
J
Kudo
Masataka
M
Sherwood
O David
OD
Hsueh
Aaron J W
AJ
D000262:Adenylyl Cyclases / Q000378:metabolism; D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D000242:Cyclic AMP / Q000378:metabolism; D018076:DNA, Complementary; D005260:Female; D020869:Gene Expression Profiling; D005836:Genitalia, Female / Q000378:metabolism; D006801:Humans; D007743:Labor, Obstetric / Q000187:drug effects; D008024:Ligands; D008565:Membrane Proteins; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D009928:Organ Specificity; D010446:Peptide Fragments / Q000494:pharmacology; D011247:Pregnancy; D017434:Protein Structure, Tertiary; D051381:Rats; D011956:Receptors, Cell Surface / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D043562:Receptors, G-Protein-Coupled; D018000:Receptors, Peptide / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D012065:Relaxin / Q000494:pharmacology / Q000502:physiology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction; D014162:Transfection
D018076:DNA, Complementary; D008024:Ligands; D008565:Membrane Proteins; D010446:Peptide Fragments; C417543:RXFP1 protein, human; D011956:Receptors, Cell Surface; D043562:Receptors, G-Protein-Coupled; D018000:Receptors, Peptide; D011993:Recombinant Fusion Proteins; C033395:relaxin receptors; D012065:Relaxin; D000242:Cyclic AMP; D000262:Adenylyl Cyclases