Molecular Basis of Human Salt Sensitivity: The Role of the 11β-Hydroxysteroid Dehydrogenase Type 21

Emanuela Lovati, Paolo Ferrari, Bernhard Dick, Kristin Jostarndt, Brigitte M. Frey, Felix J. Frey, Ulrike Schorr, Arya M. Sharma
1999 Journal of Clinical Endocrinology and Metabolism  
Salt-sensitive subjects (SS) increase their blood pressure with increasing salt intake. Because steroid hormones modulate renal sodium retention, we hypothesize that the activity of the 11␤-hydroxysteroid dehydrogenase type 2 (11␤HSD2) enzyme is impaired in SS subjects as compared with salt-resistant (SR) subjects. The 11␤HSD2 enzyme inactivates 11-hydroxy steroids in the kidney, thus protecting the nonselective mineralocorticoid receptor from occupation by glucocorticoids. We performed an
more » ... e performed an association study using a recently identified single AluI polymorphism in exon 3 and a polymorphic microsatellite marker of the HSD11B2 gene in 149 normotensive white males (37 SS and 112 SR). The activity of the enzyme 11␤HSD2 was assessed by determining the urinary ratio of cortisol (THFϩ5␣THF) to cortisone (THE) metabolites by gas chromatography in all the 37 SS subjects and in 37 age-and body habitus-matched SR volunteers. Mean (THFϩ5␣THF)/THE ratio was markedly elevated in SS subjects compared with SR subjects (1.51 Ϯ 0.34 vs. 1.08 Ϯ 0.26, P Ͻ 0.00001), indicating enhanced access of glucocorticoids to the mineralocorticoid receptor in SS subjects. In 58% of SS subjects this ratio was higher than the maximum levels in SR subjects. The
doi:10.1210/jcem.84.10.6098 pmid:10523024 fatcat:seltq4ocwbb3nesulh76yfb2dm