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Glucocorticoids and 11β‐hydroxysteroid dehydrogenase type 2 gene expression in the aging kidney
Author(s) -
Audigé A.,
Dick B.,
Frey B. M.,
Frey F. J.,
Corman B.,
Vogt B.
Publication year - 2002
Publication title -
european journal of clinical investigation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.164
H-Index - 107
eISSN - 1365-2362
pISSN - 0014-2972
DOI - 10.1046/j.1365-2362.2002.01003.x
Subject(s) - endocrinology , medicine , corticosterone , glucocorticoid , kidney , chemistry , excretion , gene expression , mineralocorticoid , aldosterone , biology , hormone , biochemistry , gene
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 11β‐keto compounds by the enzyme 11β‐hydroxysteroid dehydrogenase type 2 (11β‐HSD2) is one of these mechanisms. We hypothesized therefore that 11β‐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. Materials and methods Corticosterone (B) concentrations in plasma and urinary excretion of corticosterone and dehydrocorticosterone (A) tetrahydro metabolites, THB + 5α‐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 11β‐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 + 5α‐THB)/THA and free B/A and renal 11β‐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 11β‐HSD2 in these aging rats, suggesting either that endogenous 11β‐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.