Stewart P M, Whorwood C B, Barber P, Gregory J, Monder C, Franklyn J A, Sheppard M C
Department of Medicine, University of Birmingham, Queen Elizabeth Hospital, Edgbaston, United Kingdom.
Endocrinology. 1991 Apr;128(4):2129-35. doi: 10.1210/endo-128-4-2129.
In the kidney, 11 beta-dehydrogenase (11 beta-DH) converts the active steroid cortisol to inactive cortisone (corticosterone to 11-dehydrocorticosterone in the rat). In man, congenital and acquired deficiency of 11 beta-dehydrogenase are rare causes of hypertension in which cortisol acts as a potent mineralocorticoid. Observations from these clinical studies indicate that 11 beta-DH conveys specificity for the mineralocorticoid receptor in distal tubules and collecting ducts. However, while some studies do indicate 11 beta-DH activity in rat distal tubules and collecting ducts, immunohistochemical studies localize 11 beta-DH only to proximal tubules. to resolve this dilemma, we have performed in situ hybridization localization of 11 beta-DH mRNA in rat kidney tissue using 35S-labeled sense and antisense cRNA probes to rat 11 beta-DH. In contrast to our immunohistochemical studies in which 11 beta-DH protein was localized predominantly to proximal tubules in the inner cortex, 11 beta-DH mRNA was expressed in tubules in both the inner and outer cortex, most probably proximal and distal tubules, and in collecting ducts extending across the corticomedullary junction to the papillary tip. Weak hybridization was also seen in glomeruli, but no hybridization to the sense 11 beta-DH cRNA or to sections pretreated with RNase-A was observed. We conclude that renal 11 beta-DH is suitably located to prevent access of glucocorticoid to the MR in an autocrine and not a paracrine fashion. 11 beta-DH in proximal tubules may protect the glucocorticoid receptor.
在肾脏中，11β-脱氢酶（11β-DH）可将活性类固醇皮质醇转化为无活性的可的松（在大鼠中为皮质酮转化为11-脱氢皮质酮）。在人类中，先天性和后天性11β-脱氢酶缺乏是高血压的罕见病因，在此情况下皮质醇发挥强效盐皮质激素的作用。这些临床研究的观察结果表明，11β-DH赋予远曲小管和集合管中的盐皮质激素受体特异性。然而，虽然一些研究确实表明大鼠远曲小管和集合管中有11β-DH活性，但免疫组织化学研究仅将11β-DH定位于近端小管。为了解决这一困境，我们使用35S标记的大鼠11β-DH正义和反义cRNA探针，对大鼠肾组织中的11β-DH mRNA进行了原位杂交定位。与我们的免疫组织化学研究结果相反，在免疫组织化学研究中11β-DH蛋白主要定位于内皮质的近端小管，而11β-DH mRNA在内皮质和外皮质的小管中均有表达，很可能是近端和远端小管，以及延伸穿过皮质髓质交界处直至乳头尖端的集合管。在肾小球中也观察到弱杂交信号，但未观察到与11β-DH正义cRNA或经核糖核酸酶A预处理的切片的杂交信号。我们得出结论，肾脏中的11β-DH定位适当，可通过自分泌而非旁分泌方式阻止糖皮质激素与盐皮质激素受体结合。近端小管中的11β-DH可能会保护糖皮质激素受体。
