How is aldosterone synthesized from cholesterol?

Updated: Oct 19, 2018
  • Author: George P Chrousos, MD, FAAP, MACP, MACE, FRCP(London); Chief Editor: Robert P Hoffman, MD  more...
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Answer

Aldosterone is synthesized from cholesterol in a series of 6 biosynthetic steps (see the image below). Only the last 2 steps are specific to aldosterone synthesis; the first 4 also apply to cortisol synthesis by the zona fasciculata. Consequently, a defect in one of the specific aldosterone synthetic enzymes does not lead to hypercortisolism and secondary ACTH-mediated adrenal hyperplasia.

Steroid biosynthetic pathway. Steroid biosynthetic pathway.

The enzyme aldosterone synthase is encoded by the gene CYP11B2 and has 11β-hydroxylase, 18-hydroxylase, and 18-hydroxydehydrogenase activity. This gene is located on human chromosome arm 8q24.3-tel, close to the gene CYP11B1, which encodes 11β-hydroxylase, the enzyme that catalyzes the final step of cortisol synthesis. Mutations in these genes can result in a number of disorders of aldosterone synthesis (see Differentials). [2]

Aldosterone action on target tissues (eg, the distal renal tubule, sweat glands, salivary glands, and epithelium of the large intestine) is mediated via a specific mineralocorticoid receptor. Mineralocorticoid receptors exhibit equal affinity for mineralocorticoids and cortisol, yet the aldosterone receptors in the distal tubule and elsewhere are protected from cortisol-mediated activation by 11β-hydroxysteroid dehydrogenase type 2, which locally converts cortisol to inactive cortisone.


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