Anti-INSL3: Rabbit INSL3 Antibody

The receptor for INSL3 has been identified as the novel G-protein coupled receptor (GPCR) LGR8, also known as Great. This receptor is structurally closely related to the GPCR LGR7, which is now shown to be the principal receptor for relaxin in all reproductive tissues. Like the relaxin-LGR7 system, INSL3 appears to act through its receptor to induce an intracellular increase in cAMP, both in transfected cells overexpressing cloned Lgr8, and in gubernacular and prostate cells with naturally expressed receptors.² Knockout mice (Great mice), whose Lgr8 gene is deleted, have an identical cryptorchid phenotype to that of the Insl3 knockout mice, and further breeding experiments have conclusively shown that no other ligand is able to activate LGR8, nor is any other receptor able to respond to INSL3. It has been shown that LGR8 expressed by the cells of the fetal gubernacular ligament, which attaches the testis ventrally to the inguinal body wall, responds to INSL3 by causing a growth and condensation of the ligament, effectively retaining the testis in the inguinal region during the first, so-called transabdominal phase of testicular descent.³ In adults, it was demonstrated that INSL3 has a modulating effect on bone metabolism and LGR8 gene mutations may be linked with with human osteoporosis.⁴

The INSL3-LGR8 system appears to be evolutionarily relatively modern. There is no evidence for such a system in any submammalian vertebrate or invertebrate, and it would appear to have evolved parallel to the evolution of the relaxin (as opposed to relaxin-3)-LGR7 system in female physiology. Relaxin-3 is now recognized as being the ancestral hormone, is expressed predominantly in the brain, and acts through another class of GPCR (GPCR135). Thus, although the LGR7/LGR8 subfamily of GPCRs appears to be quite old, its association with relaxin and INSL3 seems to have evolved together with the development of classical mammalian traits such as a scrotal testis and viviparity.⁵