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17α-Hydroxylase/17,20-lyase (CYP17A1) !

One enzyme with two activities that decide whether pregnenolone goes to cortisol, to androgens or only to aldosterone.

Updated 2026-11-01

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Key facts

  • 17α-Hydroxylase: pregnenolone → 17-hydroxypregnenolone and progesterone → 17-hydroxyprogesterone (needed for cortisol).
  • 17,20-Lyase: cuts the side chain to form DHEA (and, to a lesser degree, androstenedione): needed for androgens and oestrogens.
  • It is in the fasciculata, reticularis and gonads but not in the glomerulosa; lyase activity rises with cytochrome b5 and phosphorylation.
  • Structure 3RUK is human CYP17A1 with abiraterone bound to the haem iron.
Also called
P450c17
EC number
1.14.14.19
Genes
CYP17A1
Structure (PDB)
3RUK

Regulation

  • ACTH in the adrenal and LH in Leydig and theca cells raise its expression.
  • Cytochrome b5 and serine phosphorylation favour 17,20-lyase activity (adrenarche).

Inhibitors and toxins

  • Abiraterone (castration-resistant prostate cancer)
  • Ketoconazole

Clinical notes

  • Its deficiency blocks cortisol, androgen and oestrogen production; 11-deoxycorticosterone and corticosterone pile up: hypertension, low potassium and absent puberty.
  • Abiraterone blocks adrenal and tumour androgen production in advanced prostate cancer; it is given with a glucocorticoid.
  • Increased 17,20-lyase activity in ovary and adrenal contributes to the androgen excess of polycystic ovaries.

Pathways

Test yourself

Think of the answer, then tap the question to see it.

Which two activities does CYP17A1 have?

17α-hydroxylase (the road to cortisol) and 17,20-lyase (the road to androgens).

Why does the zona glomerulosa make only aldosterone?

Because it does not express CYP17A1, so pregnenolone cannot go towards cortisol or androgens.

Which drug inhibits CYP17A1 in prostate cancer?

Abiraterone.

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Educational information, not medical advice. For any symptom, see a health professional.

Sources: CYP17A1: Steroid 17-alpha-hydroxylase/17,20 lyase (human) (UniProt, 2026); CYP17A1 gene: MedlinePlus Genetics (MedlinePlus, US National Library of Medicine, 2026); 3RUK: Human Cytochrome P450 CYP17A1 in complex with Abiraterone (RCSB Protein Data Bank, 2026); 17 alpha-hydroxylase/17,20-lyase deficiency: MedlinePlus Genetics (MedlinePlus, US National Library of Medicine, 2026); Textbook of Biochemistry for Medical Students, 6th ed. (Jaypee Brothers Medical Publishers (Vasudevan DM, Sreekumari S, Vaidyanathan K), 2011).

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