Glucocorticoids and 11 beta-hydroxysteroid dehydrogenase type 2 gene expression in the aging kidney.
BACKGROUND
Aging is associated with increased concentrations of circulating glucocorticoids, a situation expected to induce a glucocorticoid-mediated mineralocorticoid effect, resulting in sodium retention and hypertension unless counteracting mechanisms are operative. Conversion of glucocorticoids to inert 11 beta-keto compounds by the enzyme 11 beta-hydroxysteroid dehydrogenase type 2 (11 beta-HSD2) is one of these mechanisms. We hypothesized therefore that 11 beta-HSD2 gene expression and/or activity increase with age in male WAG/Rij rats, a strain without increased blood pressure with age or senescence-related obesity or kidney disease.


METHODS
Corticosterone (B) concentrations in plasma and urinary excretion of corticosterone and dehydrocorticosterone (A) tetrahydro metabolites, THB + 5 alpha-THB + THA, were assessed by gas chromatography-mass spectrometry (GC-MS) in 10-month-old-rats (n = 6) and in 30-month-old rats (n = 6). Renal 11 beta-HSD2 messenger ribonucleic acid (mRNA) abundance was measured by real-time quantitative TaqMan polymerase chain reaction and microarray assays.


RESULTS
Thirty-month-old rats had significantly higher corticosterone concentrations in plasma and increased urinary excretion of corticosterone and dehydrocorticosterone tetrahydro metabolites. Conversion of B to A in kidney microsomes from 30-month-old rats was moderately but not significantly increased compared with 10-month-old rats. The urinary ratios of (THB + 5 alpha-THB)/THA and free B/A and renal 11 beta-HSD2 mRNA abundance were equal in 10- and 30-month-old rats.


CONCLUSIONS
There is no evidence for an enhanced gene expression or activity of renal 11 beta-HSD2 in these aging rats, suggesting either that endogenous 11 beta-HSD2 is able to cope with the increased corticosterone concentrations characteristic of the aging process or that alternative mechanisms contribute to the maintenance of a normal sodium excretion in these animals.
Audigé
A
A
Division of Nephrology and Hypertension, University of Berne, Berne, Switzerland.
Dick
B
B
Frey
B M
BM
Frey
F J
FJ
Corman
B
B
Vogt
B
B
D043209:11-beta-Hydroxysteroid Dehydrogenase Type 2; D000375:Aging / Q000502:physiology*; D000818:Animals; D004573:Electrolytes / Q000652:urine; D008401:Gas Chromatography-Mass Spectrometry; D005786:Gene Expression Regulation; D005938:Glucocorticoids / Q000378:metabolism*; D006801:Humans; D006913:Hydroxysteroid Dehydrogenases / Q000235:genetics*; D007668:Kidney / Q000201:enzymology*; D008297:Male; D008861:Microsomes / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D051381:Rats; D011919:Rats, Inbred Strains
D004573:Electrolytes; D005938:Glucocorticoids; D006913:Hydroxysteroid Dehydrogenases; D043209:11-beta-Hydroxysteroid Dehydrogenase Type 2; C468387:HSD11B2 protein, human