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Activation of Orphan Receptors by the Hormone Relaxin
Sheau Yu Hsu,1Koji Nakabayashi,1Shinya Nishi,1Jin Kumagai,1Masataka Kudo,1O. David Sherwood,2Aaron J. W. Hsueh1*
Relaxin is a hormone important for the growth and
remodeling of reproductive and other tissues during pregnancy. Althoughbinding sites for relaxin are widely distributed, the nature ofits
receptor has been elusive. Here, we demonstrate that two orphanheterotrimeric guanine nucleotide binding protein (G
protein)-coupledreceptors, LGR7 and LGR8, are capable of
mediating the actionof relaxin through an adenosine
3',5'-monophosphate (cAMP)-dependentpathway distinct from that of the
structurally related insulinand insulin-like growth factor family
ligand. Treatment of antepartummice with the soluble ligand-binding
region of LGR7 caused parturitiondelay. The wide and divergent
distribution of the two relaxinreceptors implicates their roles in
reproductive, brain, renal,cardiovascular, and other functions.
1 Division of Reproductive Biology, Department
of Gynecology and Obstetrics, Stanford University School of Medicine,
Stanford, CA 94305, USA.
2 Department of Molecular
and Integrative Physiology, University of Illinois, Urbana-Champaign,
IL 61801, USA.
*
To whom correspondence should be addressed. E-mail:
aaron.hsueh{at}stanford.edu
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73, 1046-1056
|Abstract »|Full Text »|PDF »
The Effects of Blocking the Actions of Estrogen and Progesterone on the Rates of Proliferation and Apoptosis of Cervical Epithelial and Stromal Cells During the Second Half of Pregnancy in Rats.
Specificity and promiscuity of gonadotropin receptors.
S. Costagliola, E. Urizar, F. Mendive, and G. Vassart (2005)
Reproduction
130, 275-281
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Central Relaxin-3 Administration Causes Hyperphagia in Male Wistar Rats.
B. M. C. McGowan, S. A. Stanley, K. L. Smith, N. E. White, M. M. Connolly, E. L. Thompson, J. V. Gardiner, K. G. Murphy, M. A. Ghatei, and S. R. Bloom (2005)
Endocrinology
146, 3295-3300
|Abstract »|Full Text »|PDF »
Heterodimeric Fly Glycoprotein Hormone-{alpha}2 (GPA2) and Glycoprotein Hormone-{beta}5 (GPB5) Activate Fly Leucine-Rich Repeat-Containing G Protein-Coupled Receptor-1 (DLGR1) and Stimulation of Human Thyrotropin Receptors by Chimeric Fly GPA2 and Human GPB5.
S. Sudo, Y. Kuwabara, J.-I. Park, S. Y. Hsu, and A. J. W. Hsueh (2005)
Endocrinology
146, 3596-3604
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Splice variants of the relaxin and INSL3 receptors reveal unanticipated molecular complexity.
M. Muda, C. He, P. G.V. Martini, T. Ferraro, S. Layfield, D. Taylor, C. Chevrier, R. Schweickhardt, C. Kelton, P. L. Ryan, et al. (2005)
Mol. Hum. Reprod.
11, 591-600
|Abstract »|Full Text »|PDF »
Insulin-Like Factor 3 Serum Levels in 135 Normal Men and 85 Men with Testicular Disorders: Relationship to the Luteinizing Hormone-Testosterone Axis.
K. Bay, S. Hartung, R. Ivell, M. Schumacher, D. Jurgensen, N. Jorgensen, M. Holm, N. E. Skakkebaek, and A.-M. Andersson (2005)
J. Clin. Endocrinol. Metab.
90, 3410-3418
|Abstract »|Full Text »|PDF »
Multiple Binding Sites Revealed by Interaction of Relaxin Family Peptides with Native and Chimeric Relaxin Family Peptide Receptors 1 and 2 (LGR7 and LGR8).
M. L. Halls, C. P. Bond, S. Sudo, J. Kumagai, T. Ferraro, S. Layfield, R. A. D. Bathgate, and R. J. Summers (2005)
J. Pharmacol. Exp. Ther.
313, 677-687
|Abstract »|Full Text »|PDF »
The Trap-like Relaxin-binding Site of the Leucine-rich G-protein-coupled Receptor 7.
Ligand activated relaxin receptor increases the transcription of IGFBP-1 and prolactin in human decidual and endometrial stromal cells.
M. Tang, J. Mazella, H. Hui Zhu, and L. Tseng (2005)
Mol. Hum. Reprod.
11, 237-243
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Morphofunctional integration between skeletal myoblasts and adult cardiomyocytes in coculture is favored by direct cell-cell contacts and relaxin treatment.
L. Formigli, F. Francini, A. Tani, R. Squecco, D. Nosi, L. Polidori, S. Nistri, L. Chiappini, V. Cesati, A. Pacini, et al. (2005)
Am J Physiol Cell Physiol
288, C795-C804
|Abstract »|Full Text »|PDF »
Is the pregnancy hormone relaxin an important player in human heart failure?.
M. Kupari, T. S. Mikkola, H. Turto, and J. Lommi (2005)
Eur J Heart Fail
7, 195-198
|Abstract »|Full Text »|PDF »
Effects of relaxin on systemic arterial hemodynamics and mechanical properties in conscious rats: sex dependency and dose response.
D. O. Debrah, K. P. Conrad, L. A. Danielson, and S. G. Shroff (2005)
J Appl Physiol
98, 1013-1020
|Abstract »|Full Text »|PDF »
Bursicon, the insect cuticle-hardening hormone, is a heterodimeric cystine knot protein that activates G protein-coupled receptor LGR2.
C.-W. Luo, E. M. Dewey, S. Sudo, J. Ewer, S. Y. Hsu, H.-W. Honegger, and A. J. W. Hsueh (2005)
PNAS
102, 2820-2825
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INSL5 Is a High Affinity Specific Agonist for GPCR142 (GPR100).
C. Liu, C. Kuei, S. Sutton, J. Chen, P. Bonaventure, J. Wu, D. Nepomuceno, F. Kamme, D.-T. Tran, J. Zhu, et al. (2005)
J. Biol. Chem.
280, 292-300
|Abstract »|Full Text »|PDF »
Pharmacological Characterization of Relaxin-3/INSL7 Receptors GPCR135 and GPCR142 from Different Mammalian Species.
J. Chen, C. Kuei, S. W. Sutton, P. Bonaventure, D. Nepomuceno, E. Eriste, R. Sillard, T. W. Lovenberg, and C. Liu (2005)
J. Pharmacol. Exp. Ther.
312, 83-95
|Abstract »|Full Text »|PDF »
Early Human Preantral Follicles Have Relaxin and Relaxin Receptor (LGR7), and Relaxin Promotes Their Development.
K. Shirota, K. Tateishi, T. Koji, Y. Hishikawa, T. Hachisuga, M. Kuroki, and T. Kawarabayashi (2005)
J. Clin. Endocrinol. Metab.
90, 516-521
|Abstract »|Full Text »|PDF »
The Extent to which Relaxin Promotes Proliferation and Inhibits Apoptosis of Cervical Epithelial and Stromal Cells Is Greatest during Late Pregnancy in Rats.
H.-Y. Lee, S. Zhao, P. A. Fields, and O. D. Sherwood (2005)
Endocrinology
146, 511-518
|Abstract »|Full Text »|PDF »
Relaxin-3/Insulin-Like Peptide 5 Chimeric Peptide, a Selective Ligand for G Protein-Coupled Receptor (GPCR)135 and GPCR142 over Leucine-Rich Repeat-Containing G Protein-Coupled Receptor 7.
C. Liu, J. Chen, C. Kuei, S. Sutton, D. Nepomuceno, P. Bonaventure, and T. W. Lovenberg (2005)
Mol. Pharmacol.
67, 231-240
|Abstract »|Full Text »|PDF »
Relaxin-induced changes in renal sodium excretion in the anesthetized male rat.
A. H. Bogzil, R. Eardley, and N. Ashton (2005)
Am J Physiol Regulatory Integrative Comp Physiol
288, R322-R328
|Abstract »|Full Text »|PDF »
A Novel Circulating Hormone of Testis Origin in Humans.
C. Foresta, A. Bettella, C. Vinanzi, P. Dabrilli, M. C. Meriggiola, A. Garolla, and A. Ferlin (2004)
J. Clin. Endocrinol. Metab.
89, 5952-5958
|Abstract »|Full Text »|PDF »
Neonatal Lethality of LGR5 Null Mice Is Associated with Ankyloglossia and Gastrointestinal Distension.
H. Morita, S. Mazerbourg, D. M. Bouley, C.-W. Luo, K. Kawamura, Y. Kuwabara, H. Baribault, H. Tian, and A. J. W. Hsueh (2004)
Mol. Cell. Biol.
24, 9736-9743
|Abstract »|Full Text »|PDF »
Implantation and Pregnancy Following In Vitro Fertilization and the Effect of Recombinant Human Relaxin Administration in Macaca fascicularis.
