| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
Diederich S, Quinkler M, Miller K, Heilmann P, Schöneshöfer M, Oelkers W. Human kidney 11βhydroxysteroid dehydrogenase: regulation by adrenocorticotropin? Eur J Endocrinol 1996;134:301–7. ISSN 0804–4643
In ectopic adrenocorticotropin (ACTH) syndrome (EAS) with higher ACTH levels than in pituitary Cushing's syndrome and during ACTH infusion, the ratio of cortisol to cortisone in plasma and urine is increased, suggesting inhibition of renal 11β-hydroxysteroid dehydrogenase (11β-HSD) by ACTH or by ACTH-dependent steroids. Measuring the conversion of cortisol to cortisone by human kidney slices under different conditions, we tested the possibility of 11β-HSD regulation by ACTH and corticosteroids. Slices prepared from unaffected parts of kidneys removed because of renal cell carcinoma were incubated with unlabeled or labeled cortisol, and cortisol and cortisone were quantitated after HPLC separation by UV or radioactive detection. The 11β-HSD activity was not influenced by incubation with increasing concentrations (10–12–10–9 mol/l) of ACTH (1–24 or 1–39) for 1 h. Among 12 ACTH-dependent steroids tested (10–9–10–6 mol/l), only corticosterone (IC50 = 2 x 10–7 mol/l), 18-OH-corticosterone and 11βOH-androstenedione showed a significant dose-dependent inhibition of 11β-HSD activity. The percentage conversion rate of cortisol to cortisone was concentration dependent over the whole range of cortisol concentrations tested (10–8–10–5 mol/l). A direct inhibitory effect of ACTH on 11β-HSD is, therefore, unlikely. The only steroids inhibiting the conversion of cortisol to cortisone are natural substrates for 11β-HSD Kinetic studies show a saturation of the enzyme at high cortisol concentrations. Thus, the reduced percentage renal cortisol inactivation in EAS seems to be due mainly to overload of the enzyme with endogenous substrates (cortisol, corticosterone and others) rather than to direct inhibition of 11β-HSD by ACTH or ACTHdependent steroids, not being substrates of 11β-HSD.
S Diederich, Department of Endocrinology, Klinikum Benjamin Franklin, Freie Universität Berlin, Hindenburgdamm 30, 12200 Berlin, Germany
This article has been cited by other articles:
|
|
 |
|
  N. S. Sieber-Ruckstuhl, F. S. Boretti, M. Wenger, C. Maser-Gluth, and C. E. Reusch Serum concentrations of cortisol and cortisone in healthy dogs and dogs with pituitary-dependent hyperadrenocorticism treated with trilostane Vet Rec., October 18, 2008; 163(16): 477 - 481. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Quinkler and P. M. Stewart Hypertension and the Cortisol-Cortisone Shuttle J. Clin. Endocrinol. Metab., June 1, 2003; 88(6): 2384 - 2392. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Diederich, E. Eigendorff, P. Burkhardt, M. Quinkler, C. Bumke-Vogt, M. Rochel, D. Seidelmann, P. Esperling, W. Oelkers, and V. Bahr 11{beta}-Hydroxysteroid Dehydrogenase Types 1 and 2: An Important Pharmacokinetic Determinant for the Activity of Synthetic Mineralo- and Glucocorticoids J. Clin. Endocrinol. Metab., December 1, 2002; 87(12): 5695 - 5701. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. Heilmann, E. Buchheim, J. Wacker, and R. Ziegler Alteration of the Activity of the 11{beta}-Hydroxysteroid Dehydrogenase in Pregnancy: Relevance for the Development of Pregnancy-Induced Hypertension? J. Clin. Endocrinol. Metab., November 1, 2001; 86(11): 5222 - 5226. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Hatakeyama, S. Inaba, N. Taniguchi, and I. Miyamori Functional Adrenocorticotropic Hormone Receptor in Cultured Human Vascular Endothelial Cells : Possible Role in Control of Blood Pressure Hypertension, November 1, 2000; 36(5): 862 - 865. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. Weber, S. Lewicka, M. Deuschle, M. Colla, P. Vecsei, and I. Heuser Increased Diurnal Plasma Concentrations of Cortisone in Depressed Patients J. Clin. Endocrinol. Metab., March 1, 2000; 85(3): 1133 - 1136. [Abstract] [Full Text]
|
|
|
|
|
|
M. Quinkler, S. Johanssen, C. Großmann, V. Bähr, M. Müller, W. Oelkers, and S. Diederich Progesterone Metabolism in the Human Kidney and Inhibition of 11{beta}-Hydroxysteroid Dehydrogenase Type 2 by Progesterone and Its Metabolites J. Clin. Endocrinol. Metab., November 1, 1999; 84(11): 4165 - 4171. [Abstract] [Full Text]
|
|
|
|
 |
|
 G. Mazzocchi, G. P. Rossi, G. Neri, L. K. Malendowicz, G. Albertin, and G. G. Nussdorfer 11ß-Hydroxysteroid dehydrogenase expression and activity in the human adrenal cortex FASEB J, November 1, 1998; 12(14): 1533 - 1539. [Abstract] [Full Text]
|
|
|
|
 |
|
 S. H.M. van Uum, A. R.M.M. Hermus, P. Smits, T. Thien, and J. W.M. Lenders The role of 11{beta}-hydroxysteroid dehydrogenase in the pathogenesis of hypertension Cardiovasc Res, April 1, 1998; 38(1): 16 - 24. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. Morineau, A. Boudi, A. Barka, M. Gourmelen, F. Degeilh, N. Hardy, A. Al-Halnak, H. Soliman, J. P. Gosling, R. Julien, et al. Radioimmunoassay of cortisone in serum, urine, and saliva to assess the status of the cortisol–cortisone shuttle Clin. Chem., August 1, 1997; 43(8): 1397 - 1407. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Diederich, B. Hanke, W. Oelkers, and V. Bahr Metabolism of Dexamethasone in the Human Kidney: Nicotinamide Adenine Dinucleotide-Dependent 11{beta}-Reduction J. Clin. Endocrinol. Metab., May 1, 1997; 82(5): 1598 - 1602. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. C. White, T. Mune, and A. K. Agarwal 11{beta}-Hydroxysteroid Dehydrogenase and the Syndrome of Apparent Mineralocorticoid Excess Endocr. Rev., February 1, 1997; 18(1): 135 - 156. [Abstract] [Full Text]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
