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Reduced 11ß-Hydroxysteroid Dehydrogenase Activity in the Remaining Kidney Following Nephrectomy¹

Division of Nephrology, Department of Medicine, University Hospital of Berne, Inselspital, 3010 Berne, Switzerland

Address all correspondence and requests for reprints to: Felix J. Frey, Division of Nephrology, Freiburgstrasse 3, Inselspital, 3010 Berne, Switzerland.

Intracellular access of steroids to gluco- and mineralocorticoid receptors is regulated by reduced 11ß-hydroxysteroid dehydrogenase (OHSD) 1 and 2. These enzymes convert active 11ß-OH-steroids into inactive 11-keto-steroids. The purpose of the present study was to establish whether the 11ß-OHSD1 and 11ß-OHSD2 are modulated in the remnant kidney 24 h or 14 days after uninephrectomy (UNX) in rats. Overall, 11ß-OHSD activity was analyzed by measuring the ratio of the exogenous 11ß-OH-steroid prednisolone to its 11-keto metabolite prednisone in vivo in kidney tissue using high performance liquid chromatography. To determine which isoenzyme accounts for the changed activity 24 h after UNX, the oxidation and reduction attributable to 11ß-OHSD1 and oxidation to 11ß-OHSD2 were analyzed in total renal extracts and in isolated glomeruli, proximal convoluted tubules (PCT), cortical ascending limbs, and cortical convoluted tubules (CCT). The messenger RNA content of 11ß-OHSD1 and 11ß-OHSD2 was measured by RT-PCR in renal tissues and single segments, using glyceraldehyde-3-phosphate-dehydrogenase as an internal standard. Protein amounts of 11ß-OHSD1 and 11ß-OHSD2 were assessed by Western blot. The prednisolone/prednisone ratio increased 24 h after UNX in 9 out of 10 animals (P 0.0011), and was unchanged 14 days after UNX. 11ß-OHSD1 oxidation (P 0.032) and reduction activity (P 0.002) declined 24 h after UNX in total extracts. 11ß-OHSD1 oxidase activity was more than 3 times higher in PCT than in glomeruli, cortical ascending limbs, and CCT, and declined by 50% after UNX (P 0.001). The reductase activity did not change following UNX in PCT. 11ß-OHSD2 activity was 5–15 times higher in CCT than in the other segments, and decreased significantly after UNX (P 0.008). UNX did not affect messenger RNA and protein levels of both enzymes in total renal extracts. In conclusion, 11ß-OHSD1 and 11ß-OHSD2 are predominantly expressed in PCT and CCT, respectively, and their corresponding oxidative activities decline after UNX. Thus, the access of 11ß-glucocorticosteroids to gluco- and mineralocorticoid receptors in the remaining kidney is facilitated after UNX.

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