A bypass gateway from cholesterol to sex steroid biosynthesis circumnavigates CYP17A1.

ABSTRACT: Biosynthesis of all androgens and estrogens from cholesterol requires CYP11A1 and CYP17A1. There is no known pathway in humans or other vertebrates that circumvents CYP17A1 for androgen or estrogen biosynthesis in physiology or disease. However, CYP17A1 inhibition cannot completely inhibit androgen biosynthesis in prostate cancer. Here, we identify a surprising role for CYP51 in androgen biosynthesis that bypasses the requirement for CYP17A1. We find that an oxysterol is converted to androgens, which we confirmed with synthesis of a deuterium-labeled oxysterol precursor. Of 57 human cytochrome P450 enzymes tested, only CYP51A1 is capable of circumventing CYP17A1. Genetic studies using stable isotope tracing demonstrate that CYP51A1 is essential for biosynthesis of ¹³C-testostero

SUBMITTER: Zhu Z 

PROVIDER: S-EPMC12678803 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature