Inhibition of 11 ß-HSD. Hemodynamic and hormonal response induced by liquorice

Abstract

Introduction: The enzyme 11 ß-hydroxysteroid-dehydrogenas (11 ß-HSD) type 2 that converts the active hormone cortisol to the inactive cortisone is inhibited by glycyrrhetinic acid (GA), the active substance in liquorice. This leads to hypertension, hypokalaemia and sodium- and fluid retention, the syndrome of pseudo-hyperaldosteronism. The aim of this thesis was to further explore the hemodynamic and hormonal response to the inhibition of 11 ß-HSD by GA.Methods The hormonal effects of liquorice consumption were investigated by use of 5 different doses of GA (75, 135, 150, 270 and 540 mg). For comparison of the genders, women started the study on day 1-4 in the menstruation cycle in the last two studies. In study 4, 36 individuals consumed 150 mg GA (15 women and 21 men) of which 11 had essential hypertension. Blood pressure, blood tests and 24-hour urine samples were taken at baseline, after 2 and 4 weeks of liquorice consumption and at the end of the wash-out period.Results Daily consumption of 75 mg GA (50 gr liquorice) induced significant hemodynamic changes, the lowest dose by our knowledge reported with this effect. The hemodynamic changes due to GA showed a linear dose-response relationship. The maximal rise in blood pressure was registered after 2 weeks, not increasing with prolonged consumption, and the individual response in the group followed the normal distribution curve. Patients with hypertension increased more prominently in blood pressure than normotensive individuals independent of age, salt-sensitivity and weight. The difference in hemodynamic response between the genders was not significant although more women than men quitted the consumption due to adverse effects. The hormonal response was primarily on cortisol, aldosterone and DHEA-s. The decrease in aldosterone lead to more increased blood pressure in men than women and in hypertensive compared with normotensive individuals. Androgen changes were minor. The inconsistent change in testosterone concentration is controversial with earlier reports. Prolactin was minimally affected.Conclusion: A moderate daily dose of GA, 75 mg, is sufficient to cause hemodynamic response that has a dose-response relationship. This response follows the normal distribution curve. Subjects with essential hypertension are more sensitive to the inhibition of 11 ß-HSD by GA than normotensive subjects. This inhibition primarily affects the adrenal hormones and minimally the sex steroid hormones.