Yamamoto Y, Kawada Y, Noda M, Yamagishi M, Ishida O, Fujihira T, Shirakawa F, Morimoto I
Department of Pediatrics, University of Occupational and Environmental Health, Kitakyushu, Japan.
Endocr J. 1995 Apr;42(2):171-7. doi: 10.1507/endocrj.42.171.
We report two siblings, a 9-year-old boy and 4-year-old girl, with ACTH insensitivity. They were referred to our hospital because of pigmentation of the skin. They had normal plasma cortisol and urinary 17-OHCS levels despite markedly high plasma ACTH, and these did not respond to consecutive 3-day ACTH-Z administration, but plasma aldosterone responded normally to increased plasma renin activity after a low sodium diet. We examined the characteristics of ACTH receptors in peripheral blood mononuclear leukocytes (MNLs) obtained from the patients and their family. Adenylate cyclase generation caused by an addition of ACTH did not occur in MNLs from the patients. In studies on ACTH binding to MNLs, a lack of high-affinity ACTH binding was observed in the patients. These results suggest that the patients have a defect in ACTH binding to the receptors, resulting in ACTH insensitivity. The reason for this defect in ACTH binding remains unclear because no significant mutation in the ACTH receptor DNA sequence was detected in the MNLs of these patients.
我们报告了两名患有促肾上腺皮质激素（ACTH）不敏感的兄弟姐妹，一名9岁男孩和一名4岁女孩。他们因皮肤色素沉着被转诊至我院。尽管血浆ACTH水平显著升高，但他们的血浆皮质醇和尿17-羟皮质类固醇（17-OHCS）水平正常，且连续3天给予促肾上腺皮质激素锌（ACTH-Z）后这些指标无反应，但低钠饮食后血浆醛固酮对血浆肾素活性升高反应正常。我们检测了从患者及其家族获取的外周血单个核白细胞（MNLs）中ACTH受体的特征。患者的MNLs中加入ACTH后未出现腺苷酸环化酶生成。在ACTH与MNLs结合的研究中，观察到患者缺乏高亲和力的ACTH结合。这些结果表明患者存在ACTH与受体结合缺陷，导致ACTH不敏感。ACTH结合缺陷的原因尚不清楚，因为在这些患者的MNLs中未检测到ACTH受体DNA序列的显著突变。
