Cytochrome P450 17A1 and Cytochrome P450 11B2 (CYP17A1 and CYP11B2)

Cytochrome P450 17A1 (CYP17A1) is a steroidogenic enzyme primarily located in the adrenal cortex and gonads. It catalyzes two crucial steps in steroidogenesis: the 17α-hydroxylation of pregnenolone and progesterone, and the 17,20-lyase-mediated cleavage to form androgens such as dehydroepiandrosterone (DHEA)[4][5]. CYP17A1 is fundamental for the biosynthesis of both glucocorticoids and sex steroids. Cytochrome P450 11B2 (CYP11B2), also called aldosterone synthase, is expressed in the zona glomerulosa of the adrenal cortex. It is responsible for the 11β-hydroxylation of deoxycorticosterone, as well as further oxidation steps that culminate in the production of aldosterone, the primary mineralocorticoid hormone controlling sodium and potassium balance[3][6][8]. Both enzymes are important therapeutic targets. CYP17A1 inhibitors (such as abiraterone) are used in the treatment of castration-resistant prostate cancer, whereas CYP11B2 inhibitors are being investigated for the treatment of hypertension and primary aldosteronism[5][9]. Dual inhibitors are in development for diseases involving both androgen excess and mineralocorticoid overproduction[9]. Elevated or abnormal expression of these enzymes is associated with adrenal tumors and congenital defects leading to hormonal imbalances[2][3].

Other names

17α-hydroxylase17,20-lyaseP450c17Aldosterone synthase11β-hydroxylase type 2

CYP17A1 inhibitors decrease androgen and glucocorticoid synthesis by blocking 17α-hydroxylase and 17,20-lyase activities. CYP11B2 inhibitors block aldosterone biosynthesis by inhibiting 11β-hydroxylation and subsequent mineralocorticoid production.