A new dawn for androgens: novel lessons from 11-oxygenated C19 steroids

A further alternative androgen synthesis pathway involves the generation of 11-oxygenated C19 steroids in the adrenal cortex via CYP11B1 activity.

“A further alternative androgen synthesis pathway involves the generation of 11-oxygenated C19 steroids in the adrenal cortex via CYP11B1 activity (Figure 2A), 127”

Measuring 11-oxo-androgens shows promise as a method to assess for hyperandrogenism.

“Measuring 11-oxo-androgens shows promise as a method to assess for hyperandrogenism [144, 145].”

11KA4 serves as substrate for AKR1C3 expressed in peripheral tissues such as adipose tissue, yielding 11KT, which binds and activates human androgen receptor with affinity and potency similar to testosterone.

“11KA4 in turn serves as a substrate for AKR1C3 expressed in peripheral tissues such as adipose tissue, yielding 11KT, which binds and activates the human androgen receptor with an affinity and potency similar to that of testosterone [45,[70], [71], [72]].”

Both 11OHA4 and 11OHT may be converted to their 11-keto counterparts by the low levels of HSD11B2 present in the adrenal, though peripheral HSD11B2 may make a more significant contribution.

“Both 11OHA4 and 11β-hydroxytestosterone (11OHT) may be converted to their 11-keto counterparts by the low levels of 11β-hydroxysteroid dehydrogenase type 2 (HSD11B2) present in the adrenal, though peripheral HSD11B2 may make a more significant contribution (Pretorius et al., 2017, Turcu et al., 2016).”

The activation of 11KA4 proceeds by 17β-reduction to 11KT, followed by 5α-reduction to 11KDHT.

“Conversely, our group has shown that the activation of 11KA4 (Δ4, 17-keto) proceeds by the 17β-reduction to 11KT, followed by 5α-reduction to 11KDHT (5α,17β) (Pretorius et al., 2017) (Fig. 6).”

11KA4 is preferentially converted to 11KT by AKR1C3 and 11KT can then be 5α-reduced to yield 11KDHT.

“11KA4 is then preferentially converted to 11KT by AKR1C3 and 11KT can then be 5α-reduced to yield 11KDHT (Pretorius et al., 2017) (Fig. 6).”

CRPC is dependent on the intracrine conversion of circulating androgen precursors of adrenal origin to active androgens.

“numerous studies have shown that CRPC is dependent on the intracrine conversion of circulating androgen precursors of adrenal origin to active androgens reviewed in (Capper et al., 2016, Luu-The et al., 2008, Pretorius et al., 2017, Sharifi and Auchus, 2012).”