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A Novel Circulating Hormone of Testis Origin in Humans

Department of Histology, Microbiology, and Medical Biotechnologies, Center for Male Gamete Cryopreservation, University of Padova (C.F., A.B., C.V., P.D., A.G., A.F.), 35121 Padova, Italy; and Clinic of Obstetrics and Gynecology, University of Bologna and S. Orsola-Malpighi Hospital (M.C.M.), 40138 Bologna, Italy

Address all correspondence and requests for reprints to: Dr. Carlo Foresta, Department of Histology, Microbiology, and Medical Biotechnologies, Center for Male Gamete Cryopreservation, University of Padova, Via Gabelli 63, 35121 Padova, Italy. E-mail: carlo.foresta{at}unipd.it.

Insulin-like factor 3 (INSL3) is a member of the relaxin-insulin family, and it is expressed in pre- and postnatal Leydig cells of the testis. This peptide affects testicular descent during embryonic development, and mutations in INSL3 gene or its receptor LGR8 (leucine-rich repeat-containing G protein-coupled receptor 8)/GREAT (G protein-coupled receptor affecting testicular descent) cause cryptorchidism in humans. The expression of LGR8/GREAT in different tissues and the production of INSL3 also by adult-type Leydig cells suggest additional roles of this hormonal system in adulthood. In this preliminary report we performed the first analysis in humans of INSL3 using a novel RIA kit to measure INSL3 concentrations in serum of normal men and with different testicular pathologies. The results show that INSL3 is circulating in adult men, and it is almost exclusively of testicular origin. Subjects with severe testicular damage, such as men with severe infertility, produce low amount of INSL3, and the concentrations of this hormone seem to reflect the functional status of the Leydig cells. In particular, INSL3 concentrations may be an even more sensitive marker of Leydig cell function than testosterone itself. Analysis of men treated with different combinations of hormones of the hypothalamus-pituitary-testis axis suggests that the production of INSL3 is related to LH in a manner similar to that of the LH-testosterone axis.

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