Connell J M, Jamieson A J, Davies E, Ingram M, Soro A, Fraser R
Medical Research Council Blood Pressure Group, Therapeutics Western Infirmary, Glasgow, Scotland.
Endocr Res. 1996 Nov;22(4):691-700. doi: 10.1080/07435809609043764.
Corticosteroid 11 beta-hydroxylation is catalysed by 11 beta-hydroxylase and aldosterone synthase. Using plasma steroid ratios, the level of this process in patients with glucocorticoid-suppressible hyperaldosteronism (GSH) was compared with that in unaffected control subjects and in patients with Conn's syndrome. Based on both 11-deoxycortisol:cortisol (S:F) and 11-deoxycorticosterone:corticosterone (DOC:B) ratios, patients with GSH showed impaired resting 11 beta-hydroxylase activity. In GSH, but not in the other groups, the S:F ratio was significantly correlated with basal plasma aldosterone concentration. ACTH infusion increased the S:F ratio in all these patient groups, suggesting a common partial deficiency. The results also indicate that 11 beta-hydroxylation may be rate-limiting in normal subjects. In control subjects and patients with Conn's syndrome, the DOC:B ratio was not affected by ACTH. However, in GSH patients, this ratio fell markedly, indicating an increased efficiency of 11 beta-hydroxylation of DOC (but not S). This may be due to the activation by ACTH of the zona fasciculata chimaeric aldosterone synthase characteristic of this disease. Plasma aldosterone, corticosterone and DOC concentrations, appeared to be more sensitive to ACTH in GSH than the other groups. The defect in 11 beta-hydroxylation in GSH accounts for the increased levels of DOC reported in the condition, and may contribute to the phenotypic variability.
皮质类固醇11β-羟化由11β-羟化酶和醛固酮合酶催化。利用血浆类固醇比率，将糖皮质激素可抑制性醛固酮增多症（GSH）患者的这一过程水平与未受影响的对照受试者及原发性醛固酮增多症患者进行比较。基于11-脱氧皮质醇：皮质醇（S:F）和11-脱氧皮质酮：皮质酮（DOC:B）比率，GSH患者显示静息时11β-羟化酶活性受损。在GSH患者中，而非其他组中，S:F比率与基础血浆醛固酮浓度显著相关。促肾上腺皮质激素（ACTH）输注使所有这些患者组的S:F比率升高，提示存在共同的部分缺陷。结果还表明，11β-羟化在正常受试者中可能是限速步骤。在对照受试者和原发性醛固酮增多症患者中，DOC:B比率不受ACTH影响。然而，在GSH患者中，该比率显著下降，表明DOC（而非S）的11β-羟化效率提高。这可能是由于ACTH激活了该病特有的束状带嵌合醛固酮合酶。与其他组相比，GSH患者的血浆醛固酮、皮质酮和DOC浓度似乎对ACTH更敏感。GSH中11β-羟化缺陷解释了该病症中报道的DOC水平升高，并可能导致表型变异性。
