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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Altered anxiety and weight gain in corticotropin-releasing hormone-binding protein-deficient mice
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Altered anxiety and weight gain in corticotropin-releasing hormone-binding protein-deficient mice

机译：促肾上腺皮质激素释放激素结合蛋白缺陷小鼠的焦虑和体重增加

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摘要

Corticotropin-releasing hormone (CRH) is widely recognized as the primary mediator of the neuroen- docrine and behavioral responses to stress, including stress- induced anxiety. The biological activity of CRH and other mammalian CRH-like peptides, such as urocortin, may be modulated by CRH-binding protein (CRH-BP). To assess directly the CRH-BP function, we created a mouse model of CRH-BP deficiency by gene targeting. Basal adrenocortico- tropic hormone and corticosterone levels are unchanged in the CRH-BP-deficient mice, and the animals demonstrate a normal increase in adrenocorticotropic hormone and corti- costerone after restraint stress. In contrast, adult male CRH- BP-deficient mice show significantly reduced body weight when compared with wild-type controls. CRH-BP-deficient mice also exhibit a significant increase in anxiogenic-like behavior as assessed by the elevated plus maze and defensive withdrawal tests. The increased anorectic and anxiogenic-like behavior most likely is caused by increased "free" CRH and/or urocortin levels in the brain of CRH-BP-deficient animals, suggesting an important role for CRH-BP in main- taining appropriate levels of these peptides in the central nervous system.
机译：促肾上腺皮质激素释放激素（CRH）被广泛认为是神经内分泌学和对压力（包括压力引起的焦虑）的行为反应的主要介体。 CRH和其他哺乳动物CRH样肽（如尿皮质激素）的生物活性可以通过CRH结合蛋白（CRH-BP）调节。为了直接评估CRH-BP功能，我们通过基因定位创建了CRH-BP缺乏症的小鼠模型。在缺乏CRH-BP的小鼠中，基础肾上腺皮质激素和皮质酮水平未发生变化，并且动物在约束性应激后表现出正常水平的肾上腺皮质激素和皮质甾酮增加。相反，与野生型对照相比，成年雄性CRH-BP缺陷型小鼠表现出明显降低的体重。 CRH-BP缺陷型小鼠还表现出显着增加的类似焦虑症的行为，如高架迷宫和防御性戒断试验所评估。厌食和类焦虑症行为的增加很可能是由于CRH-BP缺陷动物的大脑中“游离” CRH和/或尿皮质素水平升高所致，这表明CRH-BP在维持这些水平中的重要作用中枢神经系统中的肽。

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