Administration of glycyrrhetinic acid: significant correlation between serum levels and the cortisol/cortisone-ratio in serum and urine

Abstract

In vitro, cortisol and aldosterone have a similar affinity to the mineralocorticoid receptor. The 11beta-hydroxysteroid dehydrogenase catalyzes the interconversion of cortisol to its inactive 11-oxo-metabolite cortisone. This interconversion is responsible for the in vivo specificity of the mineralocorticoid receptor. A defect of this enzyme leads to a pseudohyperaldosteronism with hypertension and hypokalemia, the so-called apparent mineralocorticoid excess syndrome. Glycyrrhetinic acid, a compound of licorice, also leads to pseudohyperaldosteronism by an inhibition of the 11beta-hydroxysteroid dehydrogenase. We studied the pharmacokinetics of glycyrrhetinic acid and its effect on the 11beta-hydroxysteroid dehydrogenase. Ten healthy students, aged 24 to 38 years, were included in the study. On the first day 500 mg glycyrrhetinic acid were given orally at 08.00 h. Blood and urine samples were taken prior to and 2, 4, 7, 10 and 24 hours after ingestion of glycyrrhetinic acid. We measured the serum level of cortisol, cortisone and glycyrrhetinic acid and the urinary excretion rates of cortisol, cortisone and their 20-dihydrometabolites. For determination of glycyrrhetinic acid and steroid levels we used a fully automated liquid chromatographic analyzer which allows the highly specific and simultaneous determination of steroid profiles even in the matrix of urine. Ratios of the 11-hydroxy- and 11-oxo-metabolites were calculated and correlated to the serum level of glycyrrhetinic acid. We found a significant correlation of the steroid-ratios to the serum levels of glycyrrhetinic acid. Coefficients of correlation were 0.9873, 0.7812, 0.7396 and 0.5844 between the serum level of glycyrrhetinic acid and the cortisol/cortisone-ratio in serum (p < 0.0001), the cortisol/cortisone-ratio in urine (p = 0.0279), the 20alpha-dihydrocortisol/20alpha-dihydrocortisone-ratio in urine (p = 0.0119) and the 20beta-dihydrocortisol/20beta-dihydrocortisone-ratio in urine (p = 0.0419), respectively. We conclude that the ratios of cortisol to cortisone and of the 20-dihydrometabolites of cortisol to the 20-dihydrometabolites of cortisone provide a simple noninvasive tool for monitoring the in-vivo activity of the 11beta-hydroxysteroid dehydrogenase.

An HPLC method for the determination of the free cortisol/cortisone ratio in human urine

“…The measurement of the urinary free cortisol-cortisone ratio has been reported to be a sensitive indicator of renal 11 β-HSD 2 activity (Palermo et al, 1996;Heilmann et al, 1999). This enzyme is essential for maintaining corticoid hypokalemia with hypertension being the major symptom (Quinkler and Stewart, 2003).…”

Serum Cortisol-to-Cortisone Ratio and Blood Pressure in Severe Obesity before and after Weight Loss

“…The serum cortisol-to-cortisone (F/E) ratio is a marker of net 11βHSD activity [14] , which changes in some settings, such as inflammatory conditions [15] or after the administration of the 11βHSD2 inhibitor found in licorice [14] . If dysregulated cortisol metabolism contributes to OAH, then the F/E ratio might correlate with BP in obese patients, and changes in the F/E ratio might parallel BP reductions during weight loss.…”

A possible involvement of 3-monoglucuronyl-glycyrrhetinic acid, a metabolite of glycyrrhizin (GL), in GL-induced pseudoaldosteronism

“…Several investigations have reported that GA induces sodium retention, hypokalemia and hypertension, which are symptoms of pseudoaldosteronism, in clinical and experimental studies Serra et al, 2002;Monder et al, 1989) and also an elevation of the cortisol/cortisone-ratio in serum and urine in healthy volunteers (Heilmann et al, 1999). It is also well known that GA inhibits human 11β-hydroxysteroiddehydrogenase (11β-HSD) (Bujalska et al, 1997).…”