ANDROGEN BIOSYNTHESIS

Androgens (testosterone and 5α-dihydrotestosterone) belong to the group of steroid hormones. The major circulating androgen is testosterone, which is synthesized from cholesterol in the Leydig cells in the testis. Testosterone production in the fetal human testis starts during the sixth week of pregnancy. Leydig cell differentiation and the initial early testosterone biosynthesis in the fetal testis are independent of luteinizing hormone (LH) (5, 6, 7). During testis development production of testosterone comes under the control of LH which is produced by the pituitary gland. Synthesis and release of LH is under control of the hypothalamus through gonadotropin-releasing hormone (GnRH) and inhibited by testosterone via a negative feedback mechanism (8).The biosynthetic conversion of cholesterol to testosterone involves several discrete steps, of which the first one includes the transfer of cholesterol from the outer to the inner mitochondrial membrane by the steroidogenic acute regulatory protein (StAR) and the subsequent side chain cleavage of cholesterol by the enzyme P450scc (9). This conversion, resulting in the synthesis of pregnenolone, is the rate-limiting step in testosterone biosynthesis. Subsequent steps require several enzymes including, 3β-hydroxysteroid dehydrogenase, 17α-hydroxylase/C17-20-lyase and 17β-hydroxysteroid dehydrogenase type 3[Figure 3] (10).

Figure 3. Biosynthetic pathway of testicular Testosterone synthesis.

Biosynthetic pathway of testicular Testosterone synthesis.