Kyossev Z, Walker P D, Reeves W B
Division of Nephrology, University of Arkansas for Medical Sciences, Little Rock, USA.
Kidney Int. 1996 Jan;49(1):271-81. doi: 10.1038/ki.1996.39.
The inactivation of physiological glucocorticoids by 11 beta-hydroxysteroid dehydrogenase (11 beta-HSD) confers mineralocorticoid specificity to certain aldosterone target tissues. Both NADP, and NAD-dependent isoforms of 11 beta-HSD have been described. An NAD-dependent isoform of 11 beta-HSD (11 beta-HSD2) was recently cloned from human kidney. The present studies were designed to examine the cellular distribution of 11 beta-HSD2 in human kidney and colon, and to determine if the cellular distribution of 11 beta-HSD2 within the human kidney and colon is consistent with a role in conferring mineralocorticoid specificity. Using antibodies against a fusion protein containing a portion of the human 11 beta-HSD2, immunohistochemical staining of human kidney showed intense, specific staining of connecting tubules and cortical and medullary collecting tubules and less intense staining in the cortical thick ascending limb. No immunoreactivity was found in proximal tubules, glomeruli, or blood vessels. Within the collecting tubules staining was heterogeneous. The majority of cells showed intense cytoplasmic staining while alpha-intercalated cells displayed much less immunoreactivity. Within the colon, 11 beta-HSD2 immunoreactivity was found predominantly in surface epithelial cells but not in submucosal tissues. Thus, the distribution of the cloned NAD-dependent 11 beta-HSD2 parallels the distribution of mineralocorticoid receptors within the kidney and colon. These results support the view that the NAD-dependent isoform of 11 beta-HSD (11 beta-HSD2) provides mineralocorticoid specificity by inactivating glucocorticoids in an autocrine fashion.
11β-羟基类固醇脱氢酶（11β-HSD）使生理性糖皮质激素失活，赋予某些醛固酮靶组织盐皮质激素特异性。已描述了11β-HSD的NADP依赖性和NAD依赖性同工型。最近从人肾中克隆出NAD依赖性的11β-HSD同工型（11β-HSD2）。本研究旨在检测11β-HSD2在人肾和结肠中的细胞分布，并确定11β-HSD2在人肾和结肠内的细胞分布是否与赋予盐皮质激素特异性的作用一致。使用针对含人11β-HSD2一部分的融合蛋白的抗体，人肾免疫组织化学染色显示连接小管、皮质和髓质集合小管有强烈的特异性染色，而皮质厚升支染色较弱。在近端小管、肾小球或血管中未发现免疫反应性。在集合小管内，染色不均一。大多数细胞显示强烈的细胞质染色，而α-闰细胞显示的免疫反应性要少得多。在结肠内，11β-HSD2免疫反应性主要见于表面上皮细胞，而不见于黏膜下组织。因此，克隆的NAD依赖性11β-HSD2的分布与肾和结肠内盐皮质激素受体的分布相似。这些结果支持这样一种观点，即NAD依赖性的11β-HSD同工型（11β-HSD2）通过以自分泌方式使糖皮质激素失活来提供盐皮质激素特异性。
