STEROID-HORMONES AND HYPERTENSION - THE CORTISOL-CORTISONE SHUTTLE

The role of adrenal steroid hormones in hypertension has, until recent ly, focused on disorders of secretion. We describe a new form of miner alocorticoid hypertension which arises from impaired metabolism of phy siological glucocorticoid. 11 beta-hydroxysteroid dehydrogenase (11 be ta-HSD) is responsible for the inactivation of cortisol to cortisone. Congenital absence of this enzyme (the syndrome of apparent mineraloco rticoid excess) results in cortisol acting as a potent mineralocortico id. Furthermore, inhibition of this enzyme by glycyrrhizic and glycyrr hetinic acids also accounts for the mineralocorticoid excess states se en following licorice and carbenoxolone ingestion. Whilst impaired 11 beta-HSD activity has been shown in patients with ''essential'' hypert ension, the significance of this finding remains unknown. These clinic al studies, however, have uncovered a novel physiological mechanism, w hereby the mineralocorticoid receptor (which in vitro has an equal aff inity for cortisol and aldosterone) is protected from cortisol excess by the action of 11 beta-HSD. Thus 11 beta-HSD plays a crucial role in determining the in vivo specificity for this receptor.