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Endocrinology, Vol 135, 101-106, Copyright © 1994 by Endocrine Society
ARTICLES |
G Escher, FJ Frey and BM Frey
Division of Nephrology, University Hospital of Berne, Inselspital, Switzerland.
The purpose of the present investigation was to establish whether the ratio of the biologically active prednisolone to its inactive metabolite prednisone is determined by the 11 beta-hydroxysteroid dehydrogenase (11 beta-OHSD). The concentration ratios of prednisolone/prednisone assessed by HPLC 60 min after ip administration of prednisolone to rats were 0.8 in kidney, 5.5 in lung, 5.7 in spleen, 6.3 in heart, 7.1 in plasma, and 43 in liver. When prednisolone was injected together with glycyrrhetinic acid, an inhibitor of the 11 beta- OHSD, the ratios of prednisolone/prednisone in plasma and all tissues increased more than 10-fold. The plasma concentrations of glycyrrhetinic acid required to exhibit apparent half-maximal inhibitory effect of the 11 beta-OHSD were more than 7-fold higher for renal than for all other tissues. Thus, the 11 beta-OHSD accounts for low prednisolone/prednisone concentration ratios in renal tissue and, therefore, has to be considered a relevant determinant for the local intrarenal immunosuppressive effect of 11 beta-hydroxysteroids such as prednisolone.
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