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Abstract
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.