Abstract
Background: Impaired 11β-hydroxysteroid dehydrogenase type 2 (11β-HSD2) has been suggested in patients with hypertension or renal disease, where it may contribute to sodium retention and hypertension. 11β-HSD1, which is expressed predominantly in liver and adipose tissue, influences glucose homeostasis and fat distribution by altering intracellular cortisol (F) concentrations. We tested immunosuppressive drugs that cause hypertension, and substances that interfere with steroidogenesis or influence glucose homeostasis for their ability to influence the inhibition of 11β-HSD isozymes.
Methods: For inhibition experiments, we used microsomes prepared from unaffected parts of human liver segments and resected human kidney cortex because of hepatocarcinoma or renal cell cancer. The inhibitory potency of several compounds was evaluated in concentrations from 10-9 -10-5 mol/l.
Results: Only sirolimus, but not cyclosporine A, tacrolimus, mycophenolate mofetil, or azathioprine showed a slight inhibition of 11β-HSD2 activity. None of the drugs that inhibit steroidogenesis (suramine, mitotane, etomidate, and aminogluthethimide) or steroid metabolism (rifampicine) influenced 11β-HSDs, nor did ginsenoides Re, Rc, and Rb1. Among sulfonylureas, only gliclazide decreased significantly 11β-HSD1 activity.
Conclusions: Increased blood pressure due to immunosuppressive drugs is probably not caused by direct inhibition of 11β-HSD2. An additional glucose lowering effect of sulfonylurea gliclazide may be due to its ability to inhibit 11β-HSD1.
Key words
11β-hydroxysteroid - dehydrogenases - aldosterone - cortisol - drugs - obesity - sulfonylureas - mineralocorticoid receptor
References
Correspondence
marcus.quinkler@charite.de
