Paracrine and endocrine roles of insulin-like factor 3.

Insulin-like factor 3 (INSL3) is expressed in Leydig cells of the testis and theca cells of the ovary. This peptide affects testicular descent by acting on gubernaculum via its specific receptor leucine-rich repeat-containing G protein-coupled receptor 8 (LGR8). From initial animal data showing the cryptorchid phenotype of Insl3/Lgr8 mutants, an extensive search for mutations in INSL3 and LGR8 genes was undertaken in human patients with cryptorchidism, and a frequency of mutation of 4-5% has been detected. However, definitive proofs of a causative role for some of these mutations are still lacking. More recent data suggest additional paracrine (in the testis and ovary) and endocrine actions of INSL3 in adults. INSL3 circulates at high concentrations in serum of adult males and its production is dependent on the differentiation effect of LH. Therefore, INSL3 is increasingly used as a specific marker of Leydig cell differentiation and function.