NAD(+)-dependent isoform of 11 beta-hydroxysteroid dehydrogenase. Cloning and characterization of cDNA from sheep kidney.
11 beta-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 M(r) of 46,700. When expressed in oocytes, this enzyme functions as an NAD(+)-dependent 11 beta-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 17 beta-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.
Agarwal
A K
AK
Department of Pediatrics, New York Hospital-Cornell Medical Center, New York 10021.
Mune
T
T
Monder
C
C
White
P C
PC
D042842:11-beta-Hydroxysteroid Dehydrogenases; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D003001:Cloning, Molecular; D018076:DNA, Complementary / Q000302:isolation & purification*; D006913:Hydroxysteroid Dehydrogenases / Q000737:chemistry / Q000235:genetics* / Q000502:physiology; D007527:Isoenzymes / Q000235:genetics*; D007668:Kidney / Q000201:enzymology*; D007700:Kinetics; D008969:Molecular Sequence Data; D009243:NAD / Q000502:physiology*; D009693:Nucleic Acid Hybridization; D012756:Sheep
D018076:DNA, Complementary; D007527:Isoenzymes; D009243:NAD; D006913:Hydroxysteroid Dehydrogenases; D042842:11-beta-Hydroxysteroid Dehydrogenases