TY - JOUR
T1 - NAD+-dependent Isoform of 11β-Hydroxysteroid Dehydrogenase
T2 - Cloning and Characterization of cDNA from Sheep Kidney
AU - Agarwal, Anil K.
AU - Mune, Tomoatsu
AU - Monder, Carl
AU - White, Perrin C.
N1 - Copyright:
Copyright 2004 Elsevier B.V., All rights reserved.
PY - 1994/10/21
Y1 - 1994/10/21
N2 - 11β-Hydroxysteroid dehydrogenase (11-HSD) catalyzes the conversion of cortisol to cortisone and corticosterone to 11-dehydrocorticosterone. This activity may be required to confer normal ligand specificity upon the mineralocorticoid receptor. Although an isozyme of 11-HSD was previously isolated from rat liver, a different isozyme is apparently expressed in mineralocorticoid target tissues. We isolated a sheep kidney cDNA clone encoding this isozyme by expression screening using Xenopus oocytes. The cDNA is 1.8 kilobase pairs in length and encodes a protein of 427 amino acid residues with a predicted Mr of 46,700. When expressed in oocytes, this enzyme functions as an NAD+-dependent 11β-dehydrogenase with very high affinity for steroids, but it has no detectable reductase activity. It is 37% identical in amino acid sequence to an NAD+-dependent isozyme of 17β-hydroxysteroid dehydrogenase but only 20% identical to the NADP+-dependent liver isozyme of 11-HSD. It is expressed at high levels in the kidney and adrenal and at lower levels in the colon. The corresponding gene is present in a single copy in the sheep genome. In humans, this gene is a candidate locus for the syndrome of apparent mineralocorticoid excess, a form of hypertension postulated to result from 11-HSD deficiency in mineralocorticoid target tissues.
AB - 11β-Hydroxysteroid dehydrogenase (11-HSD) catalyzes the conversion of cortisol to cortisone and corticosterone to 11-dehydrocorticosterone. This activity may be required to confer normal ligand specificity upon the mineralocorticoid receptor. Although an isozyme of 11-HSD was previously isolated from rat liver, a different isozyme is apparently expressed in mineralocorticoid target tissues. We isolated a sheep kidney cDNA clone encoding this isozyme by expression screening using Xenopus oocytes. The cDNA is 1.8 kilobase pairs in length and encodes a protein of 427 amino acid residues with a predicted Mr of 46,700. When expressed in oocytes, this enzyme functions as an NAD+-dependent 11β-dehydrogenase with very high affinity for steroids, but it has no detectable reductase activity. It is 37% identical in amino acid sequence to an NAD+-dependent isozyme of 17β-hydroxysteroid dehydrogenase but only 20% identical to the NADP+-dependent liver isozyme of 11-HSD. It is expressed at high levels in the kidney and adrenal and at lower levels in the colon. The corresponding gene is present in a single copy in the sheep genome. In humans, this gene is a candidate locus for the syndrome of apparent mineralocorticoid excess, a form of hypertension postulated to result from 11-HSD deficiency in mineralocorticoid target tissues.
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M3 - Article
C2 - 7929304
AN - SCOPUS:0028081325
SN - 0021-9258
VL - 269
SP - 25959
EP - 25962
JO - Journal of Biological Chemistry
JF - Journal of Biological Chemistry
IS - 42
ER -