Cortisol, 11beta-hydroxysteroid dehydrogenases, and hypertension.
Hypersecretion of cortisol is associated with hypertension. In addition, an abnormal cortisol metabolism may play a role in the pathogenesis of hypertension. The 11beta-hydroxysteroid dehydrogenase (11beta-HSD) isozymes catalyze interconversion of cortisol and cortisone and play an important role in the regulation of the effects of cortisol. Activity of 11beta-HSD type 2, converting active cortisol in inactive cortisone, is crucial in preventing access of cortisol to the renal mineralocorticoid receptors (MRs). Decreased activity of this isozyme in the kidney, either congenitally in Apparent Mineralocorticoid Excess syndrome or acquired following licorice consumption, allows cortisol access to the MRs, resulting in hypokalemic hypertension. In normotensive subjects, an association has been demonstrated between blood pressure increase on a high-salt diet and a mild decrease of renal 11beta-HSD2 activity. In ectopic adrenocorticotropic hormone (ACTH), plasma cortisol levels are very high, resulting in mineralocorticoid hypertension caused by saturation of the available renal 11beta-HSD2 capacity. Activity of the 11beta-HSDs has also been demonstrated in many extrarenal sites. Several studies have demonstrated extrarenal effects of cortisol on blood pressure, as well as a possible role for altered extrarenal 11beta-HSD activities in the pathogenesis of hypertension. More studies are needed to clarify the role of 11beta-HSDs in the pathogenesis of hypertension.
Division of Endocrinology and Metabolism, Department of Medicine, University of Western Ontario, London, Ontario, Canada.
Stan H M
SH
van Uum
Jacques W M
JW
Lenders
Ad R M M
AR
Hermus
D042842:11-beta-Hydroxysteroid Dehydrogenases / Q000502:physiology*; D000818:Animals; D001794:Blood Pressure / Q000502:physiology; D003480:Cushing Syndrome / Q000503:physiopathology; D005333:Fetus / Q000502:physiology; D006035:Glycyrrhiza; D006801:Humans; D006854:Hydrocortisone / Q000097:blood* / Q000378:metabolism; D006973:Hypertension / Q000097:blood / Q000503:physiopathology*; D006977:Hypertension, Renal / Q000097:blood / Q000503:physiopathology; D007668:Kidney / Q000503:physiopathology; D007676:Kidney Failure, Chronic / Q000503:physiopathology; D010920:Placenta / Q000502:physiology; D018161:Receptors, Mineralocorticoid / Q000502:physiology
D018161:Receptors, Mineralocorticoid; D042842:11-beta-Hydroxysteroid Dehydrogenases; D006854:Hydrocortisone