RENAL 11-BETA-HYDROXYSTEROID DEHYDROGENASE - A MECHANISM ENSURING MINERALOCORTICOID SPECIFICITY
RENAL 11-BETA-HYDROXYSTEROID DEHYDROGENASE - A MECHANISM ENSURING MINERALOCORTICOID SPECIFICITY
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DOI：
10.1159/000181808
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发表时间：
1990-09-01
期刊：
影响因子：
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通讯作者：
EDWARDS, CRW
中科院分区：
文献类型：
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作者：
EDWARDS, CRW
体外对盐皮质激素受体(MR)的研究表明，它们是非特异性的，并且不区分糖皮质激素(人类的皮质醇，啮齿动物的皮质酮)和醛固酮。这些发现与体内的醛固酮选择性形成了对比。我们对11-β-羟基类固醇脱氢酶(11-β-OHSD；将皮质醇转化为皮质醇或皮质酮转化为11-脱氢皮质酮)先天缺陷和继发于甘草或甘草酮的后天缺陷的研究表明，该酶在保护MR免受糖皮质激素暴露中起着至关重要的作用。11-β-OHSD在近端和远端肾单位的定位表明，它既有自分泌作用，也有旁分泌作用。在蟾蜍膀胱中存在这种保护机制表明，它至少有3亿年的历史。
In vitro studies with mineralocorticoid receptors (MR) have shown that they are non-specific and do not distinguish between glucocorticoids (cortisol in man, corticosterone in rodents) and aldosterone. These findings contrast with in vivo aldosterone selectivity. Our studies on the congenital deficiency of the enzyme 11-beta-hydroxysteroid dehydrogenase (11-beta-OHSD; which converts cortisol to cortisone or corticosterone to 11-dehydrocorticosterone) and acquired deficiency secondary to liquorice or carbenoxolone indicate that this enzyme plays a crucial role in protecting the MR from glucocorticoid exposure. The localisation of 11-beta-OHSD in both the proximal and distal nephron suggests that it has both an autocrine and a paracrine role. The presence of this protective mechanism in the toad bladder suggests that it is at least 300 million years old.