Reduced 11beta-hydroxysteroid dehydrogenase activity in experimental nephrotic syndrome

Détails

ID Serval
serval:BIB_242DE6D9AD24
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
Reduced 11beta-hydroxysteroid dehydrogenase activity in experimental nephrotic syndrome
Périodique
Nephrology, Dialysis, Transplantation
Auteur(s)
Vogt  B., Dick  B., Marti  H. P., Frey  F. J., Frey  B. M.
ISSN
0931-0509 (Print)
Statut éditorial
Publié
Date de publication
05/2002
Volume
17
Numéro
5
Pages
753-8
Notes
Journal Article
Research Support, Non-U.S. Gov't --- Old month value: May
Résumé
BACKGROUND: The disease state of the nephrotic syndrome is characterized by abnormal renal sodium retention that cannot be completely explained by a secondary hyperaldosteronism for the following reasons. Firstly, in rats an enhanced sodium retention is observed before proteinuria with intravascular volume depletion occurs. Secondly, in patients with the nephrotic syndrome, volume expansion with hypertension has been reported despite suppression of the renin-aldosterone system. Therefore, another mechanism for sodium retention must be postulated for this disease state. We hypothesize that this mechanism is a reduced 11beta-hydroxysteroid dehydrogenase 2 (11beta-HSD2) activity, a phenomenon known to cause enhanced access of cortisol or corticosterone to the mineralocorticoid receptor. METHODS: We assessed the 11beta-HSD activity by measuring the urinary ratio of tetrahydrocorticosterone (THB) plus 5alpha-tetrahydrocorticosterone (5alpha-THB) to 11-dehydro-tetrahydrocorticosterone (THA) by gas chromatography-mass spectrometry in rats with puromycin aminonucleoside (PAN)-induced proteinuria and with adriamycin nephrosis. Furthermore, the plasma ratios of corticosterone to 11-dehydrocorticosterone were measured. RESULTS: The urinary ratio of (THB+5alpha-THB)/THA increased in all animals following injection of PAN or adriamycin, indicating a reduced activity of 11beta-HSD. The reduced activity of 11beta-HSD was confirmed by an increased plasma ratio of corticosterone to 11-dehydrocorticosterone. The changes in the glucocorticoid metabolite ratios were already present before significant proteinuria appeared. CONCLUSION: PAN- or adriamycin-treated rats develop proteinuria with a reduced activity of 11beta-HSD, a mechanism contributing to the abnormal sodium retention in nephrotic syndrome.
Mots-clé
11-beta-Hydroxysteroid Dehydrogenases Animals Corticosterone/*analogs & derivatives/blood/urine Doxorubicin Hydroxysteroid Dehydrogenases/*antagonists & inhibitors Male Nephrosis/chemically induced/urine Nephrotic Syndrome/blood/*enzymology/urine Protein Isoforms/urine Proteinuria/chemically induced/urine Puromycin Aminonucleoside Rats Rats, Wistar Sodium/urine
Pubmed
Web of science
Open Access
Oui
Création de la notice
25/01/2008 14:03
Dernière modification de la notice
20/08/2019 14:02
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