Steroid hormones and hypertension: the cortisol-cortisone shuttle.
The role of adrenal steroid hormones in hypertension has, until recently, focused on disorders of secretion. We describe a new form of mineralocorticoid hypertension which arises from impaired metabolism of physiological glucocorticoid. 11 beta-hydroxysteroid dehydrogenase (11 beta-HSD) is responsible for the inactivation of cortisol to cortisone. Congenital absence of this enzyme (the syndrome of apparent mineralocorticoid excess) results in cortisol acting as a potent mineralocorticoid. Furthermore, inhibition of this enzyme by glycyrrhizic and glycyrrhetinic acids also accounts for the mineralocorticoid excess states seen following licorice and carbenoxolone ingestion. Whilst impaired 11 beta-HSD activity has been shown in patients with "essential" hypertension, the significance of this finding remains unknown. These clinical studies, however, have uncovered a novel physiological mechanism, whereby the mineralocorticoid receptor (which in vitro has an equal affinity 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.
Stewart
P M
PM
Department of Medicine, University of Birmingham, Queen Elizabeth Hospital, Edgbaston, United Kingdom.
Whorwood
C B
CB
Walker
B R
BR
D042842:11-beta-Hydroxysteroid Dehydrogenases; D000818:Animals; D002229:Carbenoxolone / Q000494:pharmacology; D003348:Cortisone / Q000378:metabolism*; D006035:Glycyrrhiza; D006801:Humans; D006854:Hydrocortisone / Q000378:metabolism*; D006913:Hydroxysteroid Dehydrogenases / Q000172:deficiency / Q000378:metabolism; D006973:Hypertension / Q000209:etiology* / Q000378:metabolism; D008661:Metabolism, Inborn Errors / Q000378:metabolism / Q000503:physiopathology; D008901:Mineralocorticoids / Q000378:metabolism; D010946:Plants, Medicinal; D018161:Receptors, Mineralocorticoid / Q000378:metabolism
D008901:Mineralocorticoids; D018161:Receptors, Mineralocorticoid; D006913:Hydroxysteroid Dehydrogenases; D042842:11-beta-Hydroxysteroid Dehydrogenases; D002229:Carbenoxolone; D003348:Cortisone; D006854:Hydrocortisone