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. Author manuscript; available in PMC: 2015 Apr 4.
Published in final edited form as: Oncogene. 2014 May 19;34(14):1745–1757. doi: 10.1038/onc.2014.115

Figure 2.

Figure 2

Canonical and alternative androgen biosynthesis pathways. Androgens are synthesized from cholesterol via multiple enzymatic steps, most of which are catalyzed by members of the cytochrome P450 (CYP) family. CYP11A1 is responsible for side chain cleavage of cholesterol, converting cholesterol to pregnenolone. Pregnenolone is then metabolized to dehydro-epiandrosterone (DHEA) and androstenedione (AD) via CYP17A1, which catalyzes both the 17 α-hydroxylation and the subsequent 17,20-lyase cleavage. The ‘canonical pathway’ for testosterone synthesis involves conversion of the major adrenal androgen DHEA and AD to testosterone in the testis, followed by irreversible 5α-reduction of testosterone to the higher affinity ligand DHT by 5α-reductases (SRD5A). 5α-reduction of upstream steroids, as opposed to 5α-reduction of testosterone, leads to DHT synthesis that bypasses testosterone through at least two pathways. In the ‘androstanedione pathway’, AD may be converted to 5-androstanedione by SRD5A that can then be converted into DHT by 17βHSD(s). Another alternative pathway to DHT occurs when 17-hydroxyprogesterone accumulates and SRD5A enzymes are present. In this alternative or ‘backdoor’ pathway, 17-hydroxyprogesterone is 5α- and 3α- reduced before the 17,20-lyase reaction of CYP17A1, yielding the 5α-reduced androgen androsterone. This pathway yields DHT without using DHEA, AD and testosterone as intermediates.