Reduced 11beta-hydroxysteroid dehydrogenase activity in experimental nephrotic syndrome.

Abstract

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.

• Authors: Bruno Vogt, Bernhard Dick, Hans-Peter Marti, Felix J Frey, Brigitte M Frey
• Journal: Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association (Nephrol Dial Transplant) Vol. 17 Issue 5 Pg. 753-8 (May 2002) ISSN: 0931-0509 [Print] England
• PMID: 11981059 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Protein Isoforms
• Puromycin Aminonucleoside
• tetrahydrocorticosterone
• Doxorubicin
• Sodium
• Hydroxysteroid Dehydrogenases
• 11-beta-Hydroxysteroid Dehydrogenases
• 11-dehydrocorticosterone
• Corticosterone

Topics

• 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)