The foetal Leydig Cell population arises shortly after testicular differentiation around 7 weeks in a human after gestation by the Human Chorionic Gonadotropin (hcG), this is known as the first wave (45). These cells function, mainly to produce androgens which are essential for masculinization of the foetus as well as in the descent of the testes in the scrotum, these androgens subsequently act as paracrine factors within the seminiferous tubules, testosterone, is only first detected around 6-7 weeks of gestation and peaks around 13-14 weeks (45). In cases where Leydig cells fail to develop or fail to produce androgens, pseudohermaphrodism occurs (46). The androgen produced ensures the Wolffian duct is maintained and there is…show more content… Postnatal differentiation of human Leydig cells involves a variety of cellular cascades resulting in mature Leydig cells. When the ‘second wave’ occurs after 2-3 months of birth there is a gradual increase in testosterone levels, the neonatal cell population during this time frame is a mix of mature well-developed Leydig cells and smaller ones (52). These cells possess well-developed steroidogenic machinery expressing both the LH receptor and key steroidogenic enzymes such as 3βHSD, P450scc, P450c17 required for androgen synthesis (53). The neonatal androgen surge is believed to play a role in imprinting various cell types in the prostate, hypothalamus, genetalia and kidney, in such a way they respond appropriately to androgen stimulation during adulthood (54). The Leydig cells then regress and testis remain dormant until puberty (55).
Following a prolonged childhood period of steroidogenic quiescence, the hypothalamus generates a pulse of GnRH around the 12th year (56). The onset GnRH typically occurs at night and is due in part to the gradual decline in nocturnal melatonin secretion from the pineal gland (56). This GnRH triggers release of the pituitary gonadotropin LH that ultimately stimulates the Leydig cells to grow in number and size, whilst also maturing and differentiating to