Licorice, computer-based analyses of dehydrogenase sequences, and the regulation of steroid and prostaglandin action

Abstract

Licorice, an ingredient in candy, chewing gum and medicines, has provided an important clue in discovering a novel mechanism that regulates the actions of mineralocorticoids in mammals (Stewart et al., 1987). This insight came as a result of an unexpected and initially unexplainable effect of licorice in causing sodium retention in some humans; that is, licorice acted like the major human mineralocorticoid aldosterone. Identification of the active principle in licorice as glycyrrhetinic acid, which has a structure with some resemblance to steroids (Fig. l), raised the possibility that licorice acted by a mechanism that involved the mineralocorticoid receptor. However, neither glycyrrhetinic acid nor its carbohydrate-containing analog, glycyrrhizic acid, binds steroid receptors with sufficient affinity to make it likely that the mineralocorticoid effect was due to an inherent steroid-like activity (Ulmann et al., 1975; Armanini et al., 1983). Soon thereafter, studies on mineralocorticoid receptors revealed another puzzling finding: both endogenous glucocorticoids (e.g. cortisol and corticosterone) and the mineralocorticoid aldosterone had similar affinities for the receptor that regulated sodium and potassium transport in the kidney (Beaumont and Fanestil, 1983; Krozowski