Cortisol, hypertension and obesity: the role of 11 beta-hydroxysteroid dehydrogenase.
AME has been a crucial experiment of biology from which much has been learnt about corticosteroid hormone action and mineralocorticoid hypertension. 11 beta-HSD is an important pre-receptor pathway determining corticosteroid hormone action. Any tissue expressing 11 beta-HSD1 or 11 beta-HSD2 can clearly modulate glucocorticoid and mineralocorticoid action independent of circulating concentrations. A series of related enzymes operates in a similar fashion to determine hormone action for other members of the thyroid/steroid hormone receptor superfamily (e.g. 17 beta-HSD, 25-hydroxyvitamin D 1 alpha-hydroxylase, aromatase, 5'-deiodinase, 5 alpha-reductase). Endocrinologists have been obsessed with measuring the concentrations of a hormone in the circulation and making their decisions on the basis of these results, whether or not that hormone is involved in the pathogenesis of a disease process. Such an approach needs to be revised, with greater emphasis on considering the action of a hormone within a given tissue and, in turn, on the role of these enzymes in the pathogenesis of human disease.
Stewart
P M
PM
University of Birmingham, Queen Elizabeth Hospital.
D042842:11-beta-Hydroxysteroid Dehydrogenases; D000328:Adult; D002648:Child; D003345:Corticosterone / Q000378:metabolism*; D046508:Culture Techniques; D005260:Female; D005333:Fetus / Q000201:enzymology; D006801:Humans; D006854:Hydrocortisone / Q000235:genetics / Q000378:metabolism*; D006913:Hydroxysteroid Dehydrogenases / Q000378:metabolism*; D006973:Hypertension / Q000201:enzymology*; D007231:Infant, Newborn; D008297:Male; D009765:Obesity / Q000201:enzymology*; D010920:Placenta / Q000201:enzymology; D012680:Sensitivity and Specificity
D006913:Hydroxysteroid Dehydrogenases; D042842:11-beta-Hydroxysteroid Dehydrogenases; D003345:Corticosterone; D006854:Hydrocortisone