Regulation of 11beta-hydroxysteroid dehydrogenase enzymes by dietary sodium in the rat.
11Beta-hydroxysterold dehydrogenase enzymes (11beta-HSD1, 11beta-HSD2) regulate access of adrenocorticosteroids to receptors. 11Beta-HSD2 is a dehydrogenase that protects mineralocorticoid receptors from circulating glucocorticoid hormones, 11beta-HSD1 is a reductase that promotes formation of active hormone in glucocorticoid-sensitive tissues. Here we investigate whether low or high sodium diets affect 11beta-HSD enzyme activities and mRNA expression in liver and kidney tissues. 11Beta-HSD activity was measured as dehydrogenation of 3H-corticosterone by microsomes in the presence of NAD or NADP. In situ hybridisation techniques were used to assess expression of 11beta-HSD1 mRNA (liver and kidney) and 11beta-HSD2 mRNA (kidney). Dietary sodium did not affect 11beta-HSD2 mRNA expression in collecting tubules of the medulla: 11beta-HSD1 mRNA in proximal tubules of the inner cortex/outer medulla was lower after a high sodium diet. 11Beta-HSD1 mRNA in liver was unaffected by treatment. Renal enzyme activity with NAD (11beta-HSD2 cofactor) was lower following a high sodium diet (P < 0.05). In the presence of NADP (11beta-HSD1 co-factor), neither renal nor hepatic activities were affected. Dietary sodium restriction appears to increase 11beta-HSD activity by a non-genomic mechanism; this should enhance aldosterone specificity for mineralocorticoid receptors. 11Beta-HSD1 mRNA expression varies independent of enzyme activity and is not clearly related to altered glucocorticoid activity.
McKinnell
J
J
Molecular Medicine Centre, University of Edinburgh, Western General Hospital, UK.
Roscoe
D
D
Holmes
M C
MC
Lloyd-MacGilp
S A
SA
Kenyon
C J
CJ
D042842:11-beta-Hydroxysteroid Dehydrogenases; D000818:Animals; D004039:Diet, Sodium-Restricted; D006728:Hormones / Q000097:blood; D006913:Hydroxysteroid Dehydrogenases / Q000235:genetics / Q000378:metabolism*; D007527:Isoenzymes / Q000235:genetics / Q000378:metabolism; D007668:Kidney / Q000033:anatomy & histology / Q000201:enzymology / Q000378:metabolism; D008099:Liver / Q000033:anatomy & histology / Q000201:enzymology / Q000378:metabolism; D008297:Male; D009929:Organ Size / Q000187:drug effects; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012964:Sodium / Q000494:pharmacology*; D014018:Tissue Distribution
D006728:Hormones; D007527:Isoenzymes; D012333:RNA, Messenger; D012964:Sodium; D006913:Hydroxysteroid Dehydrogenases; D042842:11-beta-Hydroxysteroid Dehydrogenases