Isoprenaline Reverses Glycyrrhizic Acid - Induced Inhibition of 11Beta-hydroxysteroid Dehydrogenase Bioactivity

Abstract

Glycyrrhizic acid (GCA) exerts its effect by inhibiting 11beta-hydroxysteroid dehydrogenase (11$-HSD) which catalyses the oxidation of cortisol to cortisone in man and corticosterone (B) to 11-dehydrocorticosterone (A) in rats. This GCA induced inhibition of 11$-HSD activity can be overcome by repetitive stress. Since catecholamines are among the mediators of stress, this study was carried out to determine the effect of isoprenaline on GCA-induced inhibition 11$-HSD bioactivity. Intact male Sprague Dawley rats received either drinking solution containing 1 mg/ml GCA or tap water for 10 days. On the day of killing, the rats received an intraperitoneal injection of vehicle, isoprenaline or propranolol. Hypothalamus, liver and kidney homogenates were assayed for 11$-HSD1 and 11$-HSD2 bioactivity by determining the percentage conversion of B to A in the presence of NADP and NAD respectively. Isoprenaline or propranolol had no effect on basal activity of 11$-HSD in all tissues. Isoprenaline reversed the GCA induced inhibition of 11$-HSD1 activity in the hypothalamus and kidney, whereas in the liver it reversed the GCA induced inhibition of both 11$-HSD1 and 11$-HSD2. Thus, catecholamines may be one of the mediators opposing inhibition of 11$-HSD by GCA during stress.