The mineralocorticoid receptor, expressed in cortical collecting duct cells, is the means through which aldosterone mediates potassium and proton secretion while enhancing sodium reabsorption via the ENac. It turns out that cortisol can also interact with (and activate) the mineralocorticoid receptor–however it does not usually do so based on the presence of the enzyme 11-beta-hydroxysteroid dehydrogenase type 2, which chemically modifies cortisol such that it is unable to interact with the mineralocorticoid receptor. The GZA compound in European licorice inhibits 11-beta-hydroxysteroid dehydrogenase, thereby allowing endogenous cortisol levels to constantly signal via the mineralocorticoid receptor.
The end-result is the production of
- Metabolic alkalosis
- Increased extracellular volume as a result of enhanced sodium reabsorption.
These effects are reversible upon withdrawal of licorice. The condition is sometimes called “pseudoprimary aldosteronism” since it presents clinically like primary hyperaldosteronism, but differs in that serum and urine aldosterone levels are low and serum renin activity is low (in contrast to primary hyperaldosteronism, where serum & urine aldo levels are high).
Not only is GZA present in licorice, but it also used sometimes used in chewing tobacco. The European Union suggests that people should not consume any more than 100mg of GZA a day, equivalent to about 50 grams of licorice sweets.