Stress-induced behaviors require the corticotropin-releasing hormone (CRH) receptor, but not CRH
Stress-induced behaviors require the corticotropin-releasing hormone (CRH) receptor, but not CRH
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DOI：
10.1073/pnas.96.14.8283
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发表时间：
1999-07-06
影响因子：
11.1
通讯作者：
Majzoub, JA
中科院分区：
文献类型：
--
作者：
Weninger, SC;Dunn, AJ;Majzoub, JA
促肾上腺皮质激素释放激素（CRH）是激素应激反应的中心调节因子，引起促肾上腺皮质激素和糖皮质激素分泌的刺激。CRH也被广泛认为是介导应激诱导的行为，这意味着激素在心理应激反应中具有更广泛的综合作用。缺乏CRH基因的小鼠表现出正常的应激诱导行为，该行为被CRH 1型受体拮抗剂特异性阻断。另一种已知的CRH受体的哺乳动物配体是尿皮质素。正常和CRH缺陷小鼠具有相同的尿皮质素mRNA分布，其局限于Edinger-Westphal核的区域，并且在已知介导应激相关行为的区域中不存在。由于Edinger-Westphal核不知道投射到任何被认为在焦虑样行为中发挥作用的大脑区域，因此必须假设Edinger-Westphal核中的尿皮质素通过完全不同的途径来介导CRH缺陷小鼠的这些行为。或者，一种未鉴定的CRH样分子，而不是CRH或尿皮质素，通过CRH受体在大脑区域发挥作用，被认为是介导应激诱导的行为，可能介导对应激的行为反应，单独或与CRH一起。
Corticotropin-releasing hormone (CRH) is a central regulator of the hormonal stress response, causing stimulation of corticotropin and glucocorticoid secretion. CRH is also widely believed to mediate stress-induced behaviors, implying a broader, integrative role for the hormone in the psychological stress response. Mice lacking the CRH gene exhibit normal stress-induced behavior that is specifically blocked by a CRH type 1 receptor antagonist. The other known mammalian ligand for CRH receptors is urocortin, Normal and CRH-deficient mice have an identical distribution of urocortin mRNA, which is confined to the region of the Edinger-Westphal nucleus, and is absent from regions known to mediate stress-related behaviors. Since the Edinger-Westphal nucleus is not known to project to any brain regions believed to play a role in anxiety-like behavior, an entirely different pathway must be postulated for urocortin in the Edinger-Westphal nucleus to mediate these behaviors in CRH-deficient mice. Alternatively, an unidentified CRH-like molecule other than CRH or urocortin, acting through the CRH receptors in brain regions believed to mediate stress-induced behaviors, may mediate the behavioral response to stress, either alone or in concert with CRH.