TISSUE-SPECIFIC DISTRIBUTION OF THE NAD+-DEPENDENT ISOFORM OF 11-BETA-HYDROXYSTEROID DEHYDROGENASE

被引:114
作者
WALKER, BR
CAMPBELL, JC
WILLIAMS, BC
EDWARDS, CRW
机构
关键词
D O I
10.1210/en.131.2.970
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
11-beta-hydroxysteroid dehydrogenase (11-beta-OHSD) converts the active glucocorticoid corticosterone to inactive 11-dehydrocorticosterone in rat (or cortisol to cortisone in man), thereby protecting renal mineralocorticoid receptors from corticosterone or cortisol and allowing preferential access for aldosterone. Recent work suggests that a nicotinamide adenine dinucleotide (NAD+)-dependent 11-beta-OHSD isoform is expressed in distal renal tubule, in contrast with the hepatic isoform which is NAD+-phosphate (NADP+)-dependent. To establish the distribution of the NAD+-dependent isoform we measured in vitro conversion of [H-3]corticosterone to [H-3] 11-dehydrocorticosterone in homogenized rat tissues in the presence of NADP+ or NAD+. In most tissues (liver, testis, hippocampus, heart, aorta, mesenteric artery) NADP+ increased activity and NAD+ was without effect. However, in whole renal cortex, colon, placenta, and lung both NADP+ and NAD+ increased activity. No difference in cofactor utilization was demonstrated between proximal and distal renal tubules following density gradient separation. This distribution of NAD+-dependent activity corresponds with: (i) the distribution of multiple mRNA and/or protein species of 11-beta-OHSD; (ii) the distribution of aldosterone-specific mineralocorticoid receptors; and (iii) the equilibrium between active and inactive glucocorticoids in each tissue. We suggest that the tissue-specific expression of isoforms of 11-beta-OHSD with different kinetic properties confers on them diverse roles in modulating corticosteroid receptor activation.
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页码:970 / 972
页数:3
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