织和拮抗孕酮代谢产物的性质在人类的盐皮质激素受体。
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Quinkler M, Meyer B, C Bumke-Vogt Grossmann C,格鲁伯U, Oelkers W, Diederich年代,巴尔V
织和拮抗孕酮代谢产物的性质在人类的盐皮质激素受体。
欧元2002年J性。146年6月,(6):789 - 99。
- PubMed ID
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12039699 (在PubMed]
- 文摘
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目的:孕激素结合人类的盐皮质激素受体(hMR)与醛固酮和皮质醇几乎相同的亲和力,但只授予低争胜活动。目前还不清楚如何醛固酮可以作为盐皮质激素孕酮浓度高的情况下,如怀孕。一种机制可以转换的孕激素活性化合物在hMR目标组织。设计:我们分析了16孕激素的受体激动剂和拮抗剂活动代谢物的绑定特性评估transactivation hMR以及功能研究。方法:我们研究了亲和力使用hMR表达T7-coupled兔网织红细胞溶解产物系统。我们使用的co-transfection hMR表达载体和荧光素酶报告基因在会阴细胞研究格斗和敌对的属性。结果:孕激素和11 beta-oh-progesterone (11 beta-oh-p)显示略高亲和力比皮质醇,去氧皮质酮和醛固酮。20 alpha-dihydro (DH) - p 5 alpha-dh-p和17 alpha-oh-p效力低3到10倍的绑定。所有其他孕酮代谢产物显示hMR弱关联。20 alpha-dh-p代谢物中表现出最强的格斗能力测试,醛固酮transactivation达到11.5%。 The agonistic activity of 11beta-OH-P, 11alpha-OH-P and 17alpha-OH-P was 9, 5.1 and 4.1% respectively. At a concentration of 100 nmol/l, progesterone, 17alpha-OH-P and 20alpha-DH-P inhibit nearly 75, 40 and 35% of the transactivation by aldosterone respectively. All other progesterone metabolites tested demonstrate weaker affinity, and agonistic and antagonistic potency. CONCLUSIONS: The binding affinity for hMR and the agonistic and antagonistic activity diminish with increasing reduction of the progesterone molecule at C20, C17 and at ring A. We assume that progesterone metabolism to these compounds is a possible protective mechanism for hMR. 17alpha-OH-P is a strong hMR antagonist and could exacerbate mineralocorticoid deficiency in patients with congenital adrenal hyperplasia.