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Steroid hormone synthesis (overview) !

The adrenals, ovaries, testes and placenta turn cholesterol into steroid hormones; everything starts with pregnenolone.

Updated 2026-11-01

Key facts

  • The rate-limiting step is cholesterol entry into the mitochondrion via StAR, regulated by ACTH, LH or angiotensin II.
  • CYP11A1 (side-chain cleavage enzyme) turns cholesterol into pregnenolone, the common precursor.
  • Adrenal cortex: glomerulosa → aldosterone; fasciculata → cortisol; reticularis → androgens.
  • Gonads: testosterone (testis) and oestradiol (ovary, via aromatase); the placenta makes progesterone.

In detail

  • Cholesterol comes from LDL, from ester stores in lipid droplets or from local synthesis.
  • StAR moves it to the inner mitochondrial membrane, where CYP11A1 cuts the side chain: pregnenolone (C21).
  • ER and mitochondrial P450s (17α-hydroxylase, 21-hydroxylase, 11β-hydroxylase, aldosterone synthase) and 3β-HSD set each tissue's product.
  • Androgens (C19) are converted to oestrogens (C18) by aromatase.
  • Vitamin D also comes from cholesterol, starting from 7-dehydrocholesterol in the skin.
  • The adrenal enzymes and their deficiencies (congenital adrenal hyperplasia) will get their own chapter.

Clinical notes

  • 21-Hydroxylase deficiency is the most common cause of congenital adrenal hyperplasia.
  • Ketoconazole and other P450 inhibitors reduce cortisol production.
  • StAR deficiency (lipoid adrenal hyperplasia) blocks all steroid hormones.

Pathways

Test yourself

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

What is the rate-limiting step of steroid hormone synthesis?

Cholesterol entry into the mitochondrion via StAR, followed by cleavage by CYP11A1.

Which molecule is the common precursor of all steroid hormones?

Pregnenolone.

Which hormone does each adrenal cortex zone make?

Glomerulosa: aldosterone; fasciculata: cortisol; reticularis: androgens.

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

Sources: Metabolism of steroid hormones (R-HSA-196071) (Reactome, 2026); Glucocorticoid biosynthesis (R-HSA-194002) (Reactome, 2026); Textbook of Biochemistry for Medical Students, 6th ed. (Jaypee Brothers Medical Publishers (Vasudevan DM, Sreekumari S, Vaidyanathan K), 2011).

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Representative model, for educational purposes only.