title: Enhanced 11beta-hydroxysteroid dehydrogenase activity, the metabolic syndrome, and systemic hypertension.
abstract: Metabolic syndrome, with its attendant cardiovascular complications, is reaching epidemic proportions worldwide; hence, there is intense interest in understanding the pathogenesis of and developing therapy for these common disorders. Recent studies have suggested that metabolic syndrome may be a stress response, with an underlying abnormality in the enzyme 11beta-hydroxysteroid dehydrogenase. At the cellular level, the enzyme hydroxysteroid dehydrogenase type 1 (HSD1) locally regenerates active cortisol from inactive cortisone, amplifying glucocorticoid receptor activation and promoting preadipocyte differentiation and adipocyte hypertrophy. Although initial studies in transgenic mice and humans are encouraging, more data are required to conclusively prove the hypothesis that the adipose-tissue-specific overexpression of HSD1 and the resultant increase in tissue-specific cortisol concentrations result in human obesity, insulin resistance, high blood pressure, and metabolic syndrome. Currently, selective inhibitors of HSD1 are not available for human use; however, their development is under way. The use of potent and selective HSD1 inhibitors will finally confirm or refute this hypothesis and may turn out to be an effective strategy for combating these common maladies.
authors.affiliation: Division of Cardiovascular Medicine, University of Arkansas for Medical Sciences, Little Rock, Arkansas, USA.
authors.forename: Rishi
authors.initials: R
authors.lastname: Sukhija
authors.forename: Priyanka
authors.initials: P
authors.lastname: Kakar
authors.forename: Vimal
authors.initials: V
authors.lastname: Mehta
authors.forename: Jawahar L
authors.initials: JL
authors.lastname: Mehta
mesh_terms: D042842:11-beta-Hydroxysteroid Dehydrogenases / Q000097:blood*; D000818:Animals; D015415:Biomarkers / Q000097:blood; D006801:Humans; D006973:Hypertension / Q000201:enzymology* / Q000209:etiology; D024821:Metabolic Syndrome / Q000150:complications / Q000201:enzymology*; D051379:Mice; D012307:Risk Factors
chemical_list: D015415:Biomarkers; D042842:11-beta-Hydroxysteroid Dehydrogenases