Figure 6.

Disposition pathways of steroid metabolism and the alternative pathway to DHT. Hepatic 5α-reduction, predominantly by the type 1 isoform, is a first step on the path towards excretion of Δ ⁴-3-ketosteroids as glucuronides and sulfates. The endocrine biosynthetic pathway from progesterone through testosterone (Fig. 3) is shown on the gray background to the left. The disposition pathways culminate in the formation of androsterone (and etiocholanolone via a parallel 5ß-reduced pathway) as water-soluble conjugates. Key fetal tissues express versions of this pathway that permit genital tissue to form DHT from androsterone, rather than testosterone; this constitutes the “backdoor” pathway to DHT. 17-Hydroxyallopregnanolone conversion to androsterone does not require CYB5, and both reductive and oxidative 3αHSD activities of AKR1C2/4 and 17ßHSD6 (retinol dehydrogenase/3α-hydroxysteroid epimerase) are required for this pathway.

Based on Miller and Auchus (10), Flück et al (54), and Janner et al (167).