title: 11 beta-Hydroxysteroid dehydrogenase: a link between the dysregulation of cortisol metabolism and hypertension.
abstract: Endocrine pathology is a well-recognised and important cause of human hypertension. Recent research has highlighted the role of 11 beta-hydroxysteroid dehydrogenase (11 beta-HSD) in the development of certain forms of hypertension. This enzyme, which exists as two genetically unique isoforms, 11 beta-HSD1 and 11 beta-HSD2, is responsible for the interconversion of biologically active cortisol with its inactive 11-oxo derivative, cortisone. Congenital deficiency of 11 beta-HDS2 results in inappropriate activation of the renal mineralocorticoid receptor by cortisol, leading to hypertension, hypokalaemia and metabolic alkalosis. Several authors have postulated a link between changes in 11 beta-HSD activity and the development of certain forms of essential hypertension. The existence of endogenous inhibitors of the enzyme provides compelling evidence in favour of this hypothesis, but few have been able to demonstrate a clear link between inhibition of 11 beta-HSD2 activity and hypertension by this mechanism. Similarly, several authors have suggested a relationship between reduced placental 11 beta-HSD2 activity, low birth weight with high placental weight, and the development of hypertension in adulthood. However, no clear evidence to suggest a direct correlation between birth weight, placental weight and 11 beta-HSD2 activity has been demonstrated. While the role of 11 beta-HSD in the development of hypertension remains controversial, an understanding of the interplay of this enzyme with both mineralocorticoid and glucocorticoid receptors undoubtedly will yield data that will clarify this complex field.
authors.affiliation: School of Pharmacy and Biomedical Sciences, University of Portsmouth, England, UK.
authors.forename: S J
authors.initials: SJ
authors.lastname: Donovan
mesh_terms: D042842:11-beta-Hydroxysteroid Dehydrogenases; D006801:Humans; D006854:Hydrocortisone / Q000378:metabolism*; D006913:Hydroxysteroid Dehydrogenases / Q000502:physiology*; D006973:Hypertension / Q000201:enzymology* / Q000378:metabolism; D011965:Receptors, Glucocorticoid / Q000502:physiology; D018161:Receptors, Mineralocorticoid / Q000502:physiology
chemical_list: D011965:Receptors, Glucocorticoid; D018161:Receptors, Mineralocorticoid; D006913:Hydroxysteroid Dehydrogenases; D042842:11-beta-Hydroxysteroid Dehydrogenases; D006854:Hydrocortisone