INSL3 is a member of the relaxin-insulin family, and it is expressed in pre- and postnatal Leydig cells of the testis in a variety of mammalian species, including humans. This peptide affects testicular descent during embryonic development by acting on gubernaculum via its specific receptor LGR8. From initial animal data showing the cryptorchid phenotype of Insl3/Lgr8 mutants, an extensive search for mutations in the INSL3 and LGR8 genes was undertaken in human patients with cryptorchidism. Six mutations in INSL3 and one in LGR8 genes have been detected exclusively in men with undescended testes, with an overall frequency of mutation in cryptorchid or ex-cryptorchid men of 4-5%. Definitive proofs of a causative role for many of these mutations are still lacking. However, the specific association with cryptorchidism actually suggests that they might be responsible for the phenotype. Apart from the role in testicular descent and cryptorchidism, more recent data suggest additional yet unidentified endocrine and paracrine actions in adults. INSL3 is produced constitutively, but in a differentiation-dependent manner by the adult Leydig cells, and its production and secretion is dependent on LH. INSL3 circulates at high concentrations in serum of adult males and it is increasingly used as a specific marker of Leydig cell differentiation and function. Research is needed to clarify the possible paracrine role of the INSL3/LGR8 system in the testis and ovary, and endocrine effects in many tissues where LGR8 expression has been identified.
Keywords: cryptorchidism, great, insl, leydig, lgr, rlf, spermatogenesis, testicular descent
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