Relaxin, the relaxin-like factor and their receptors.

In 1926 Frederick Hisaw discovered a blood-borne factor in pregnant guinea pigs that would cause relaxation of the pubic symphysis in virgin females of the species. The relaxin-like factor gene (RLF), also known as insulin-like 3 (INSL3), was recovered from a library of testicular cDNA. The function of RLF as the mediator of testicular positioning in mice was discovered by gene deletion experiments. The report that deletion of a G-protein-coupled receptor in a mouse mutant caused cryptorchidism and that relaxin and RLF and their receptors were structurally and functionally similar may well have inspired Drs. Hsueh and Sherwood to put LGR7 and relaxin together and thus, after many agonizing years of uncertainty, the relaxin receptor had yielded its identity. LGR8 was recognized as the human version of the RLF receptor and together LGR7 and LGR8, with their respective ligands, opened to detailed investigation the large and important field of G-protein activated leucine-rich repeat receptors. In the process RLF and LGR8 have yielded some general information that might contribute to our knowledge of receptor/ligand interaction, in particular the enigmatic signal initiation process.