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7-Hydroxy androstene steroids and a novel synthetic analogue with reduced side effects as a potential agent to treat autoimmune diseases.

机译:7-羟基雄烷类固醇和具有减少的副作用的新型合成类似物,可作为治疗自身免疫性疾病的潜在药物。

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摘要

The metabolome of dehydroepiandrosterone (DHEA), the most abundant adrenal steroid in the human body, includes androgens, estrogens and a series of immune regulating hormones that lack androgenic or estrogenic activity. Of these, 7-hydroxy derivatives, once considered physiologically inactive end products of metabolism, possess a combination of potent anti-inflammatory and immune modulating activity without androgenic or estrogenic capacity. Oxygenated metabolites derived from androstenediol (AED), the predominant precursor in rodents, may be responsible for many activities initially attributed to exogenous DHEA administered to rodents. We here review the discovery of these compounds in models of inflammation and autoimmune diseases, discuss the potential mode of action and trace the development of a specific synthetic derivative, which is less labile to metabolism and which may at last deliver to humans the benefits of DHEA observed in rodents.
机译:人体中最丰富的肾上腺类固醇脱氢表雄酮(DHEA)的代谢组包括雄激素,雌激素和一系列缺乏雄激素或雌激素活性的免疫调节激素。其中,7-羟基衍生物曾经被认为是生理上无活性的代谢终产物,具有有效的抗炎和免疫调节活性的组合,而没有雄激素或雌激素的能力。源自雄烯二醇(AED)的氧化代谢物(啮齿动物中的主要前体)可能与最初归因于啮齿动物的外源DHEA引起的许多活动有关。我们在这里回顾炎症和自身免疫性疾病模型中这些化合物的发现,讨论潜在的作用方式并追踪特定合成衍生物的开发,该合成衍生物对代谢的稳定性较弱,最终可能为人类带来DHEA的益处在啮齿动物中观察到。

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