REVIEW Origin, proliferation and differentiation of Leydig cells

Mammalian sex determination involves complex interacting networks of cellular and hormonal signals leading to the development of male or female phenotypes. Three main sequential processes are involved: first, the establishment of chromosomal sex at fecundation (genetic sex); second, the development of the undifferentiated gonad into either testes or ovaries (gonadal sex); and third, differentiation of male or female internal and external genitalia (phenotypic sex). Male phenotype is controlled by two testicular hormones, the anti-Müllerian hormone (AMH) secreted by fetal Sertoli cells which induces regression of the Müllerian ducts, and testosterone produced by Leydig cells which induces differentiation of the Wolffian ducts into male reproductive organs, although conversion of testosterone into dehydrotestosterone is required for masculinization of the external genitalia. In the absence of testes, and therefore in the absence of both AMH and testosterone, the Wolffian ducts regress, creating a permissive environment for the differentiation of the Müllerian ducts and, thereby, female reproductive organs.