11β-Hydroxysteroid dehydrogenase and Licorice: Mechanism

Cortisol, the primary glucocorticoid in the body binds to glucocorticoid receptors. However, given its molecular similarity to Aldosterone (mineralcorticoid) it can also bind to mineralcorticoid receptors.

Both Aldosterone and Cortisol bind the mineralocorticoid receptors with similar affinities; however, given the vastly more abundant levels of Cortisol in the systemic circulation this could lead to over stimulating of mineralocorticoid receptors.

In order to prevent this, an enzyme, 11β-Hydroxysteroid dehydrogenase (HSD-11β or 11β-HSD) coverts cortisol to its biologically inactive metabolite cortisone (which is no longer able to bind to mineralocorticoid receptors).

However, Licorice contains glycyrrhetinic acid which inhibits 11β-Hydroxysteroid dehydrogenase (HSD-11β or 11β-HSD) and allows cortisol to over stimulate mineralcorticoid receptors resulting in mineralocorticoid excess syndrome.

REFERENCES

1. Whorwood CB, Sheppard MC, Stewart PM. Licorice inhibits 11 beta-hydroxysteroid dehydrogenase messenger ribonucleic acid levels and potentiates glucocorticoid hormone action. Endocrinology. 1993 Jun;132(6):2287-92.
2. van Uum SH, Hermus AR, Smits P, Thien T, Lenders JW. The role of 11 beta-hydroxysteroid dehydrogenase in the pathogenesis of hypertension. Cardiovasc Res. 1998 Apr;38(1):16-24.