17hydroxylase1720lyase

17-hydroxylase/17,20-lyase, also known as cytochrome P450 17A1 (CYP17A1) or P450c17, is a microsomal enzyme essential to vertebrate steroidogenesis. It performs two distinct activities within a single protein: 17α-hydroxylation of pregnenolone and progesterone, and the 17,20-lyase cleavage of these 17α-hydroxylated products to yield dehydroepiandrosterone (DHEA) and androstenedione, key precursors for glucocorticoid and sex steroid biosynthesis. Through these reactions, CYP17A1 links cortisol, androgen, and estrogen pathways.

Localization and cofactors: CYP17A1 is anchored in the endoplasmic reticulum of steroidogenic tissues, including the adrenal cortex and gonads. It belongs to the cytochrome P450 superfamily and requires electron transfer from NADPH via P450 oxidoreductase. The 17,20-lyase activity is enhanced by cytochrome b5, modulating the balance between glucocorticoid and androgen production.

Genetics and expression: The enzyme is encoded by the CYP17A1 gene, located on chromosome 10q24.31. Expression is prominent in adrenal zona fasciculata and reticularis and in gonadal tissue, with activity regulated by physiological cues such as ACTH and gonadotropins.

Clinical significance: Deficiency of CYP17A1 causes combined 17α-hydroxylase and 17,20-lyase deficiency, leading to impaired cortisol and sex steroid synthesis, with mineralocorticoid excess and hypertension; females may have undervirilized or ambiguous genitalia, and males may experience undervirilization. Conversely, pharmacologic inhibition of CYP17A1 lowers androgen production and is used in treating advanced prostate cancer (e.g., abiraterone) or in combination therapies, though it can cause mineralocorticoid excess and other metabolic side effects.

This enzyme is a pivotal control point in steroidogenesis, influencing cortisol and sex steroid levels and, consequently, a range of developmental and endocrine outcomes.