Steroid 21-hydroxylase (CYP21A2) (CYP21A2)

Steroid 21-hydroxylase (CYP21A2) is a critical microsomal cytochrome P450 enzyme located in the adrenal cortex that facilitates the synthesis of essential steroid hormones (UniProt: P08514). It catalyzes the hydroxylation of progesterone and 17-hydroxyprogesterone, which are necessary steps in the production of aldosterone and cortisol, respectively (NCBI Gene: 1589). A deficiency in this enzyme is the most common cause of Congenital Adrenal Hyperplasia (CAH), leading to impaired cortisol synthesis and a compensatory increase in androgen production due to the accumulation of precursors (StatPearls: 21-Hydroxylase Deficiency). This condition can result in life-threatening salt-wasting crises and abnormal sexual development. While the enzyme is a primary focus for genetic screening and hormone replacement therapy, it is also susceptible to inhibition by certain antifungal and anesthetic agents, which can inadvertently cause adrenal suppression (PubMed: PMID 29073318). Understanding its regulation is vital for managing endocrine disorders and avoiding drug-induced adrenal insufficiency.

Other names

21-hydroxylaseCytochrome P450 21A2CYP21BSteroid 21-monooxygenaseP450-C21Cytochrome P450, family 21, subfamily A, polypeptide 2

The enzyme catalyzes the hydroxylation of steroid precursors at the C21 position, specifically converting progesterone to 11-deoxycorticosterone and 17-alpha-hydroxyprogesterone to 11-deoxycortisol. Pharmacological agents typically act as non-selective inhibitors of this cytochrome P450 activity, reducing the production of downstream glucocorticoids and mineralocorticoids.