NAD+-dependent Isoform of 11β-Hydroxysteroid Dehydrogenase

Cloning and Characterization of cDNA from Sheep Kidney

Anil K. Agarwal, Tomoatsu Mune, Carl Monder, Perrin C. White

Research output: Contribution to journalArticle

251 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)25959-25962
Number of pages4
JournalJournal of Biological Chemistry
Volume269
Issue number42
StatePublished - Oct 21 1994

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11-beta-Hydroxysteroid Dehydrogenases
Cloning
NAD
Isoenzymes
Organism Cloning
Sheep
Protein Isoforms
Complementary DNA
Mineralocorticoids
Kidney
Genes
Liver
Oocytes
Apparent Mineralocorticoid Excess Syndrome
Oxidoreductases
Tissue
Amino Acids
Mineralocorticoid Receptors
Cortisone
Corticosterone

ASJC Scopus subject areas

  • Biochemistry

Cite this

NAD+-dependent Isoform of 11β-Hydroxysteroid Dehydrogenase : Cloning and Characterization of cDNA from Sheep Kidney. / Agarwal, Anil K.; Mune, Tomoatsu; Monder, Carl; White, Perrin C.

In: Journal of Biological Chemistry, Vol. 269, No. 42, 21.10.1994, p. 25959-25962.

Research output: Contribution to journalArticle

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