Agarwal A K, Mune T, Monder C, White P C
Department of Pediatrics, New York Hospital-Cornell Medical Center, New York 10021.
J Biol Chem. 1994 Oct 21;269(42):25959-62.
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.
11β-羟基类固醇脱氢酶（11-HSD）催化皮质醇转化为可的松以及皮质酮转化为11-脱氢皮质酮。这种活性可能是赋予盐皮质激素受体正常配体特异性所必需的。尽管先前已从大鼠肝脏中分离出11-HSD的一种同工酶，但在盐皮质激素靶组织中显然表达的是另一种同工酶。我们通过使用非洲爪蟾卵母细胞进行表达筛选，从绵羊肾脏中分离出了编码这种同工酶的cDNA克隆。该cDNA长度为1.8千碱基对，编码一个由427个氨基酸残基组成的蛋白质，预测分子量为46,700。当在卵母细胞中表达时，这种酶作为一种依赖NAD⁺的11β-脱氢酶发挥作用，对类固醇具有非常高的亲和力，但没有可检测到的还原酶活性。其氨基酸序列与17β-羟基类固醇脱氢酶的一种依赖NAD⁺的同工酶有37%的同源性，但与11-HSD的依赖NADP⁺的肝脏同工酶只有20%的同源性。它在肾脏和肾上腺中高水平表达，在结肠中低水平表达。相应的基因在绵羊基因组中以单拷贝形式存在。在人类中，该基因是表观盐皮质激素过多综合征的候选基因座，这是一种推测由盐皮质激素靶组织中11-HSD缺乏导致的高血压形式。
