The role of the testicular factor INSL3 in establishing the gonadal position.

INSL3, also designated Leydig insulin-like (Ley I-L) or relaxin-like factor (RLF), belongs to the insulin-like hormone superfamily. It is expressed in pre- and postnatal Leydig cells of the testis and in postnatal theca cells of the ovary. This sexual dimorphic pattern of INSL3 expression during development led us to suggest that the INSL3 factor could play an essential role in sexual differentiation, gonadal function and germ cell development. Key insights into the role of INSL3 came from analyses of INSL3 knockout mice. These mice showed impaired development of the gubernaculum ligament, a structure that is believed to mediate transabdominal descent of the testis during male embryogenesis. In double mutant XY-mice lacking INSL3 and a functional androgen receptor, it was demonstrated that both are essential for establishment of the sexual dimorphic position of the gonads through regulation of gubernaculum development and regression of the cranial suspensory ligament (CSL) during fetal life. Defects in this developmental process can cause cryptorchidism in the male, which is a most common disorder of sexual differentiation in human.