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Relaxin research in the postgenomic era
Kazuhiro Kawamura1, Satoko Sudo, Jin Kumagai
1Division of Reproductive Health, Department of Obstetrics and Gynecology, Stanford University School of Medicine, Stanford, CA 94305-5317, USA.
Annals of the New York Academy of Sciences
|June 16, 2005
Summary
The insulin-like peptide 3 (INSL3) and its receptor LGR8 are crucial for reproductive functions. This paracrine system mediates gonadotropic actions in both ovaries and testes, impacting oocyte meiosis and male germ cell survival.
Area of Science:
- Reproductive Endocrinology
- Molecular Biology
- Genomics
Background:
- Leucine-rich repeat-containing G-protein-coupled receptors (LGRs) are homologous to hormone receptors.
- Phenotypic similarities in null mice suggest potential ligand-receptor pairings.
Purpose of the Study:
- To identify ligands for orphan LGR7 and LGR8 receptors.
- To elucidate the function of the INSL3-LGR8 system in reproductive processes.
Main Methods:
- Genomic sequence analysis to identify homologous LGR genes.
- In vitro and in vivo experiments to test ligand-receptor interactions and functional effects.
- Analysis of gene expression in ovarian and testicular cells.
Main Results:
- Relaxin activates LGR7 and LGR8; INSL3 and relaxin 3 are specific ligands for LGR8 and LGR7, respectively.
- LGR8 is expressed in oocytes and male germ cells.
- INSL3 binding to LGR8 initiates oocyte meiosis and suppresses male germ cell apoptosis.
Conclusions:
- The INSL3-LGR8 system is a critical paracrine pathway mediating gonadotropic actions.
- This system plays a vital role in both ovarian and testicular functions, including germ cell development and survival.