THE ANTIGLUCOCORTICOID AND ANTIPROGESTIN STEROID RU-486 SUPPRESSES THE ADRENOCORTICOTROPIN RESPONSE TO OVINE CORTICOTROPIN RELEASING HORMONE IN MAN
THE ANTIGLUCOCORTICOID AND ANTIPROGESTIN STEROID RU-486 SUPPRESSES THE ADRENOCORTICOTROPIN RESPONSE TO OVINE CORTICOTROPIN RELEASING HORMONE IN MAN
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DOI：
10.1210/jcem-66-2-290
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发表时间：
1988-02-01
影响因子：
5.8
通讯作者：
SCHAISON, G
中科院分区：
文献类型：
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作者：
LAUE, L;CHROUSOS, GP;SCHAISON, G
糖皮质激素和孕酮拮抗剂RU 486使非垂体库兴综合征患者皮质醇增多的临床和生化特征正常化，可能是通过拮抗皮质醇的作用。由于RU 486除了具有孕酮拮抗剂作用外，还具有孕酮激动剂活性，因此它可能具有某些糖皮质激素激动剂作用的可能性似乎并非不合理。为了验证这一假设，我们在10例原发性肾上腺皮质功能不全患者中检测了RU 486对垂体ACTH分泌的影响，这些患者停用糖皮质激素替代治疗36小时。每例患者在1800 h以随机顺序间隔3-7天接受安慰剂、RU 486（20 mg/kg）、皮质醇（0.1 mg/kg）或RU 486和皮质醇的组合口服给药。2小时后，静脉推注绵羊CRH（1 μ g/kg），连续测定血浆ACTH水平3小时。RU 486抑制绵羊CRH刺激的ACTH分泌，尽管低于皮质醇。其糖皮质激素激动剂效应计算为约1/250皮质醇的重量基础上。此外，Ru 486部分拮抗皮质醇诱导的ACTH分泌抑制。这些结果表明，RU 486是一种部分糖皮质激素激动剂，并提供了一些关于其在库兴综合征患者中的作用的见解。然而，这种程度的糖皮质激素激动剂活性是否足以维持生命尚不清楚。
The glucocorticoid and progesterone antagonist RU 486 normalizes the clinical and biochemical features of hypercortisolism in patients with nonpituitary Cushing''s syndrome, presumably by antagonizing the action(s) of cortisol. Since RU 486 has progesterone agonist activity in addition to its progesterone antagonist action, the possibility that it might have some glucocorticoid agonist action did not seem unreasonable. To test this hypothesis was examined the effects of RU 486 on pituitary ACTH secretion in 10 patients with primary adrenal insufficiency in whom glucocorticoid replacement was withheld for 36 h. Each patient received, in randomized sequence 3-7 days apart, an oral dose of placebo, RU 486 (20 mg/kg), cortisol (0.1 mg/kg), or a combination of RU 486 and cortisol at 1800 h. Two hours later, an iv bolus dose of ovine CRH (1 .mu.g/kg) was administered, and plasma ACTH levels were measured serially for 3 h. RU 486 suppressed ovine CRH-stimulated ACTH secretion, albeit less than cortisol. Its glucocorticoid agonist effect was calculated to be approximately 1/250th that of cortisol on a weight basis. Additionally, Ru 486 partially antagonized cortisol-induced suppression of ACTH secretion. These findings suggest that RU 486 is a partial glucocorticoid agonist and offer some insight as to its action in patients with Cushing''s syndrome. Whether this degree of glucocorticoid agonist activity is adequate to support life, however, is not known.