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J. Biol. Chem., Vol. 269, Issue 42, 25959-25962, Oct, 1994
AK Agarwal, T Mune, C Monder and PC White
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.
NAD(+)-dependent isoform of 11 beta-hydroxysteroid dehydrogenase. Cloning and characterization of cDNA from sheep kidney
Department of Pediatrics, New York Hospital-Cornell Medical Center, New York 10021.
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R. E. Smith, K. X. Z. Li, R. K. Andrews, and Z. Krozowski Immunohistochemical and Molecular Characterization of the Rat 11{beta}-Hydroxysteroid Dehydrogenase Type II Enzyme Endocrinology, February 1, 1997; 138(2): 540 - 547. [Abstract] [Full Text] [PDF]
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Y. H. Lo, M. F. Sheff, S. A. Latif, C. Ribeiro, H. Silver, A. S. Brem, and D. J. Morris Kidney 11{beta}-HSD2 Is Inhibited by Glycyrrhetinic Acid-Like Factors in Human Urine Hypertension, January 1, 1997; 29(1): 500 - 505. [Abstract] [Full Text] [PDF]
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P. C. White Inherited Forms of Mineralocorticoid Hypertension Hypertension, December 1, 1996; 28(6): 927 - 936. [Abstract] [Full Text]
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A. Naray-Fejes-Toth and G. Fejes-Toth Subcellular Localization of the Type 211beta -Hydroxysteroid Dehydrogenase. A GREEN FLUORESCENT PROTEIN STUDY J. Biol. Chem., June 28, 1996; 271(26): 15436 - 15442. [Abstract] [Full Text] [PDF]
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T. Mune and P. C. White Apparent Mineralocorticoid Excess : Genotype Is Correlated With Biochemical Phenotype Hypertension, June 1, 1996; 27(6): 1193 - 1199. [Abstract] [Full Text]
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B. R. Walker, R. Best, C. H.L. Shackleton, P. L. Padfield, and C. R.W. Edwards Increased Vasoconstrictor Sensitivity to Glucocorticoids in Essential Hypertension Hypertension, February 1, 1996; 27(2): 190 - 196. [Abstract] [Full Text]
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Y. Takeda, I. Miyamori, K. Iki, S. Inaba, K. Furukawa, H. Hatakeyama, T. Yoneda, and R. Takeda Endogenous Renal 11ß-Hydroxysteroid Dehydrogenase Inhibitory Factors in Patients With Low-Renin Essential Hypertension Hypertension, February 1, 1996; 27(2): 197 - 201. [Abstract] [Full Text]
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