ESPE Abstracts (2014) 82 WG3.2

The Potential Role of the Alternative 'Backdoor' Pathway for Androgen Synthesis and Virilisation in CAH

Clemens Kamrath

Justus-Liebig University, Giessen, Germany

Data from urinary steroid metabolomics approach gave evidence that the ‘backdoor’ pathway might act as a source of androgen synthesis in CAH. Although the prenatal role of this pathway in CAH is unknown, the backdoor pathway could be involved in fetal androgen metabolism and could contribute to genital virilisation. The traditional concept of androgen synthesis in CAH postulates that androstenedione acts as a precursor of testosterone and dihydrotestosterone, and that androstenedione is normally produced by metabolism of DHEA. Additionally, the Δ5 pathway via DHEA strongly predominates in the human testis and adrenal because the catalytic efficiency for the 17,20-lyase reaction of CYP17A1 is nearly 100-fold greater for Δ5 17α-hydroxypregnenolone than for Δ4 17α-hydroxyprogesterone. However, the fetal adrenal normally produces abundant DHEA which is further converted to estriol in the placenta, protecting the female fetus from virilisation. As backdoor pathway derived androgens are already 5α-reduced, they cannot be aromatized to estrogens. Therefore, this new concept of androgen synthesis via the backdoor pathway in CAH might contribute to better understanding of virilisation in CAH.

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