CYP17

CYP17A1 encodes cytochrome P450 17A1, a steroidogenic enzyme that catalyzes both 17α-hydroxylase and 17,20-lyase reactions required for glucocorticoid and sex steroid biosynthesis, thereby controlling the production of androgen precursors such as dehydroepiandrosterone (DHEA) within endocrine tissues.^[1][2] Mechanistically, CYP17A1 occupies a central position in steroidogenesis because its 17,20-lyase activity represents the first committed step in androgen biosynthesis, linking cholesterol-derived steroid intermediates to testosterone and dihydrotestosterone synthesis.^[3][4] Therefore, CYP17A1 functions as an essential regulatory node in androgen signaling pathways that support the growth and progression of castration-resistant prostate cancer (CRPC).^[5][6] In disease models, increased steroidogenic activity and persistent intracrine androgen signaling have been associated with therapeutic resistance, and CYP17A1 upregulation has been identified as one mechanism contributing to resistance against androgen biosynthesis blockade.^[5][7] Compared with related steroidogenic cytochrome P450 enzymes, CYP17A1 is distinguished by its dual catalytic activities, which determine whether steroid metabolism is directed toward glucocorticoid or sex steroid production.^[2] For experimental and therapeutic applications, CYP17A1 inhibitors such as abiraterone suppress androgen synthesis by targeting both hydroxylase and lyase activities, although concomitant inhibition of cortisol synthesis can induce mineralocorticoid-related adverse effects.^[3][8] Consequently, selective CYP17A1 lyase inhibitors have been developed to reduce androgen production while minimizing disruption of glucocorticoid homeostasis.^[3][9]