Reduced activity of 11beta-hydroxysteroid dehydrogenase type 2 is not responsible for sodium retention in nephrotic rats.
OBJECTIVE
In mineralocorticoid target cells 11-beta-hydroxysteroid dehydrogenase type 2 (11betaHSD2) converts glucocorticoids into non-active metabolites thereby protecting the mineralocorticoid receptor (MR) from stimulation by glucocorticoids. In nephrotic syndrome, a decreased activity of 11betaHSD2 has been suggested to allow glucocorticoids to stimulate MR, thereby contributing to sodium retention. We tested this hypothesis in the puromycin aminonucleoside model of nephrotic syndrome in rats.


METHODS
Complete sodium and potassium intakes and excretions (faeces and urine) were measured in rats in metabolic cages. RNase protection assay of mRNA and Western blotting of protein were used to estimate renocortical expression of 11betaHSD2 and of the MR downstream effector serum and glucocorticoid induced kinase (SGK). In an intervention series, dexamethasone was given [10 microg (100 g bw)(-1)] to suppress endogenous glucocorticoids in the proteinuric stage during active sodium retention.


RESULTS
Nephrotic rats developed proteinuria, positive sodium balance, decreased plasma aldosterone concentration, and decreased urinary Na(+)/K(+) ratio. 11betaHSD2 mRNA expression was down-regulated but protein expression was unchanged. SGK mRNA and phosphorylated SGK protein were up-regulated while total SGK protein expression was unchanged. Dexamethasone treatment, which suppressed plasma corticosterone concentration, did not correct sodium balance or fluid retention in nephrotic rats.


CONCLUSIONS
Our results do not support the hypothesis that stimulation of the MR by endogenous glucocorticoids induces sodium and fluid retention in experimental nephrotic syndrome in rats.
Bistrup
C
C
Department of Physiology and Pharmacology, University of Southern Denmark, Winsloewparken 21, Odense C, Denmark. claus.bistrup@dadlnet.dk
Thiesson
H C
HC
Jensen
B L
BL
Skøtt
O
O
D043209:11-beta-Hydroxysteroid Dehydrogenase Type 2 / Q000032:analysis / Q000378:metabolism*; D000450:Aldosterone / Q000097:blood; D000818:Animals; D003345:Corticosterone / Q000097:blood; D003907:Dexamethasone / Q000494:pharmacology; D004195:Disease Models, Animal; D015536:Down-Regulation / Q000502:physiology; D005243:Feces / Q000737:chemistry; D005938:Glucocorticoids / Q000494:pharmacology; D007672:Kidney Cortex / Q000187:drug effects / Q000378:metabolism; D008297:Male; D009404:Nephrotic Syndrome / Q000201:enzymology / Q000378:metabolism*; D010766:Phosphorylation; D011188:Potassium / Q000378:metabolism / Q000652:urine; D011507:Proteinuria / Q000201:enzymology / Q000378:metabolism; D011692:Puromycin Aminonucleoside; D012333:RNA, Messenger; D051381:Rats; D017207:Rats, Sprague-Dawley; D012964:Sodium / Q000378:metabolism* / Q000652:urine; D015854:Up-Regulation / Q000502:physiology
D005938:Glucocorticoids; D012333:RNA, Messenger; D000450:Aldosterone; D011692:Puromycin Aminonucleoside; D003907:Dexamethasone; D012964:Sodium; D043209:11-beta-Hydroxysteroid Dehydrogenase Type 2; D011188:Potassium; D003345:Corticosterone