Mineralocorticoid receptor (MR) is expressed not only in the kidney but also in cardiomyocytes, where aldosterone promotes cardiac fibrosis. The enzyme that protects renal mineralocorticoid receptors from cortisol (which has equal affinity for MR) activation is:

• A 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) — converts cortisone to cortisol in adipose and liver
• B CYP11B2 (aldosterone synthase) — converts corticosterone to aldosterone only in zona glomerulosa
• C Corticosteroid-binding globulin (CBG) — preferentially binds cortisol in renal circulation
• D 11β-hydroxysteroid dehydrogenase type 2 (11β-HSD2) — inactivates cortisol to cortisone in renal tubular cells ✓

Explanation

Cortisol circulates at concentrations ~100× those of aldosterone and has equivalent affinity for the mineralocorticoid receptor. Renal tubular cells express high levels of 11β-HSD2, which rapidly converts cortisol (active) to cortisone (inactive, cannot bind MR) in the cell cytoplasm, protecting the MR from cortisol-mediated activation. This allows aldosterone selectivity in the kidney. In apparent mineralocorticoid excess (AME), 11β-HSD2 is deficient (genetic) or inhibited (licorice/carbenoxolone contains glycyrrhizinic acid), allowing cortisol to act as a mineralocorticoid causing hypertension and hypokalemia.

Reference: Guyton & Hall, Textbook of Medical Physiology, 14th ed.

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Written and medically reviewed by the StethoPrep medical team.