CYP11

CYP11 enzymes play a pivotal role in steroidogenesis by catalyzing essential hydroxylation steps in cortisol and aldosterone biosynthesis^[1][2][3]. CYP11A1 mediates the first and rate-limiting step, converting cholesterol to pregnenolone under cAMP-dependent transcriptional regulation in adrenal cortex and gonads^[2][4][8]. CYP11B1 and CYP11B2 carry out 11β-hydroxylation in the zona fasciculata and zona glomerulosa, respectively, producing cortisol and aldosterone with isoform-specific physiological outcomes^[1][3][5][6]. Mechanistically, overproduction of cortisol by CYP11B1 contributes to Cushing's syndrome, whereas excessive aldosterone via CYP11B2 drives hypertension and end-organ damage^[1][6][10]. Compared with CYP11B1, CYP11B2 displays distinct substrate specificity and regulation, enabling selective pharmacological targeting for cardiovascular and renal disease models^[1][7][11]. In experimental applications, recombinant yeast and mammalian cell systems have been developed to screen isoform-selective inhibitors, such as SIAS-1 for CYP11B2 and emerging CYP11B1 inhibitors, facilitating preclinical evaluation of steroidogenesis modulation^[7][10]. Opevesostat, a CYP11A1 inhibitor, demonstrates translational potential in suppressing androgen-dependent tumor growth, highlighting CYP11 isoforms as viable therapeutic targets^[8][9]. Therefore, understanding the precise functional distinctions and pathway-specific roles of CYP11 isoforms informs both disease mechanism studies and the rational design of selective modulators.