(A) Front door pathway. Steroid production in the normal fetus. 3β-HSD activity is
low in the fetal adrenal gland, and the most produced adrenal steroid is DHEA (and
DHEA-S). However, small amounts of steroids go into the aldosterone and cortisol
pathways. 21-hydroxylase in the adrenal gland is required for both pathways. The
adrenal gland can produce small amounts of testosterone through the activity of
17β-HSD. (B) Backdoor pathway. If 21-hydroxylase (P450c21) is deficient, three
pathways produce androgen. The first is a pathway from cholesterol to DHEA. Large
amounts of DHEA are converted to DHEA-S and inactivated, while some DHEA is converted
to testosterone and dihydrotestosterone (DHT). In the second pathway of the normal
adrenal gland, a tiny amount of 17-OHP is converted to androstenedione, small amounts
of 17-OHP produced in CAH are converted to androstenedione, and testosterone is
produced. The third pathway is a backdoor pathway in which 17-OHP undergoes by 5α- and
3β-reduction and is converted to 17-OH allopregnanolone. This steroid is converted to
androstanediol, oxidized by 3α-HSD oxidoreductase and converted to DHT. This pathway
was first found in Marsupialia and mammals and is also present in humans based on
urine steroid analysis using mass spectrometry. This pathway is thought to be involved
in virilization of the external genitalia in girls with 21-OHD.