Renal Regulation of Extracellular Fluid Composition Symposium in Honor of Donald W. Seldin, M.D.

Kidney International (1990) 38, 673–678; doi:10.1038/ki.1990.258

Inhibition of 11bold beta-hydroxysteroid dehydrogenase and its effect on epithelial sodium transport

Klaus Hierholzer1, Harald Siebe1 and Michael Fromm1

1Institut für Klinische Physiologie, Klinikum Steglitz, Freie Universität Berlin, Berlin, Federal Republic of Germany

Correspondence: Klaus Hierholzer MD, Institut für Klinische Physiologie, Klinikum Steglitz, Freie Universität Berlin, D-1000 Berlin 45, Federal Republic of Germany.

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Abstract

Recently the hitherto accepted concept of mechanism(s) of interaction between (cortico)steroid hormones and target cells has been modified and extended. Thus, as proposed in the case of estrogen receptors, unoccupied and hormone occupied receptors exclusively reside in the nuclear compartment [1], In intact cells there is no translocation of hormone-receptor complex from cytoplasm to nuclei [2]. In enucleated preparations unoccupied receptors could be localized in the nuclear compartment.

The second notion which has attracted attention is the presence of corticosteroid metabolizing enzymes in many target tissues. It is most likely that such enzymes are included in the control of the cellular response to corticosteroid hormone signals [3, 4]. An important enzyme system, 11beta-hydroxy-steroid-dehydrogenase (11-HSD, E.C. 1.1.1.146), has recently been implicated in mediating mineralocorticoid specificity of corticosteroid receptors [5–7].1 It is this concept we address in the present paper. In experiments with rat renal microsomal fractions we have tested the inhibitory effects of steroidal inhibitors on both the apparent oxidative and reductive activity of 11-HSD. Subsequently, isolated rat rectal epithelium has been used in the attempt to test whether or not inhibition of 11-HSD might modify the apparent mineralocorticoid activity of the endogenous rat glucocorticoid corticosterone.

Abbreviations:

B =, corticosterone; 11-DHB =, 11-dehydrocorticosterone; ALDO =, aldosterone; 11-HSD =, 11beta-hydroxysteroid-dehydrogenase (E.C. 1.1.1.146); GLY =, glycyrrhetinic acid; CHAPS =, 3-[(3-cholamidopropyl)-dimethylammonio]-1-propane-sulfonate; Isc =, short circuit current (micromol dot h-1 cm-2); JNa =, amiloride sensitive Na transport (micromol dot h-1 cm-2)

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References

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