Glycyrrhetinic acid (GA) has diverse in vitro effects as an inhibitor of 11beta hydroxysteroid dehydrogenase (11HSD), 5alpha reductase and hormone receptor binding. However, in vivo GA studies have focussed on the hypertensive effects associated with the syndrome of apparent mineralocorticoid excess (SAME) in which 11HSD inhibition allows glucocorticoid hormones to bind inappropriately to MR and subsequent decreased aldosterone synthesis. Here we consider whether GAs other in vitro effects are reflected in altered steroid hormone profiles in vivo. The effect of liquorice (containing GA) has been assessed by measuring steroid hormone levels in healthy individuals. Ten men and 10 women (1830 years) were given 100 g liquorice sweets (3% liquorice extract) or non-liquorice containing confectionary for 7 days in a crossover study. Saliva was collected 30 min after waking, at 11001300 h and at 18002100 h for cortisol, cortisone, aldosterone (Aldo), deoxycorticosterone (DOC), DHEA and testosterone measurements by in-house, sensitive and specific ELISA methods. Systolic blood pressure measured at the end of the two periods of treatment showed non-significant increases (P=0.127) in response to liquorice consumption. Cortisol was significantly higher (P=0.003) and cortisone and aldo were reduced by liquorice (P<0.001) consistent with the SAME. DHEA, testosterone and DOC were increased (P<0.001) possibly because of reduced hepatic clearance. However, these steroids are not 11HSD type 2 substrates indicating liquorice might also have inhibited hepatic 5alpha reductase. Recent studies also implicate the bi-directional 11HSD type1 enzyme in DHEA metabolism. GA is equipotent as an inhibitor of 11HSD type 1 and type 2 oxidase activity. 7-Hydroxy-DHEA, a major metabolite of DHEA is inter-converted with 7-keto-DHEA by 11HSD type 1 and could, therefore, secondarily interfere with DHEA metabolism. We conclude that in addition to cortisol, other biologically active steroid hormones are affected by liquorice. Increased salivary levels of DHEA and testosterone suggest that liquorice modulates their bioavailability.
03 - 07 May 2008
European Society of Endocrinology