madman
Super Moderator
Summary
Testosterone biosynthesis is essential for the development of internal/external male genitalia, the establishment of secondary male characteristics, and spermatogenesis. Leydig cells are the primary source of testosterone in the testis. In addition to testosterone, Leydig cells produce other steroids that are essential for male development, including DHT and estradiol. In Leydig cells, testosterone and other androgens are synthesized from cholesterol derived from different sources. The translocation of cholesterol from OMM to IMM is the hormone-sensitive and rate-limiting step in androgen biosynthesis. Four steroidogenic enzymes catalyze the biosynthesis of testosterone: CYP11A1, 3b-HSD, CYP17A1, and 17b-HSD3. After synthesis, testosterone can be further metabolized into DHT, estradiol, androsterone, and 5a-androstenediol by three enzymes, 5a-reductase, CYP19A1, and 3a-HSD. Functionally different from ALCs, FLCs synthesize more DHT to support male sexual development in fetal life. There are still many unknowns about Leydig cell androgen biosynthesis, particularly so in the human. For example, the origin of human Leydig cells, the identification of individual SLCs, and the cell fate of NLCs all remain to be clarified. Moreover, it is well known that the substrate specificity of cytochrome P450s is limited, and this suggests the presence of alternative unexplored yet substrates for androgen formation (Lieberman, 2008). Investigating Leydig cell androgen biosynthesis is important in order to understand the underlying mechanisms of male sexual development and the origins of associated developmental defects. Moreover, reduced androgen formation is associated with aging.
Testosterone biosynthesis is essential for the development of internal/external male genitalia, the establishment of secondary male characteristics, and spermatogenesis. Leydig cells are the primary source of testosterone in the testis. In addition to testosterone, Leydig cells produce other steroids that are essential for male development, including DHT and estradiol. In Leydig cells, testosterone and other androgens are synthesized from cholesterol derived from different sources. The translocation of cholesterol from OMM to IMM is the hormone-sensitive and rate-limiting step in androgen biosynthesis. Four steroidogenic enzymes catalyze the biosynthesis of testosterone: CYP11A1, 3b-HSD, CYP17A1, and 17b-HSD3. After synthesis, testosterone can be further metabolized into DHT, estradiol, androsterone, and 5a-androstenediol by three enzymes, 5a-reductase, CYP19A1, and 3a-HSD. Functionally different from ALCs, FLCs synthesize more DHT to support male sexual development in fetal life. There are still many unknowns about Leydig cell androgen biosynthesis, particularly so in the human. For example, the origin of human Leydig cells, the identification of individual SLCs, and the cell fate of NLCs all remain to be clarified. Moreover, it is well known that the substrate specificity of cytochrome P450s is limited, and this suggests the presence of alternative unexplored yet substrates for androgen formation (Lieberman, 2008). Investigating Leydig cell androgen biosynthesis is important in order to understand the underlying mechanisms of male sexual development and the origins of associated developmental defects. Moreover, reduced androgen formation is associated with aging.
