The role of corticotropin-releasing factor receptors in stress and anxiety
The role of corticotropin-releasing factor receptors in stress and anxiety
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DOI：
10.1093/icb/42.3.552
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发表时间：
2002-06-01
影响因子：
2.6
通讯作者：
Vale, WW
中科院分区：
文献类型：
--
作者：
Bale, TL;Lee, KF;Vale, WW
促肾上腺皮质激素释放因子（CRF）是下丘脑-垂体-肾上腺（HPA）轴在应激反应中的重要整合因子。CRF及其相关分子尿皮质素（UCN）以不同的亲和力结合CRF受体I（CRFR 1）和CP.FR2。产生CRFR 1或CRFR 2缺陷的小鼠，以确定这些受体的生理作用。虽然CRFR 1突变小鼠显示出耗竭的应激反应并显示出抗焦虑样行为，但CRFR 2突变小鼠对应激过敏并显示出抗焦虑样行为。CRFR 1和CRFR 2突变小鼠均显示正常的基础进食和体重增加，但CRFR 2突变小鼠在食物剥夺应激后表现出食物摄入量减少。而CRFR 2突变小鼠杏仁核中央核中的CRF mRNA水平增加。CRFR 1突变小鼠在下丘脑室旁核（PVN）中表达高水平的CRF，但在cAmyg中表达正常水平。CRFR 2突变小鼠还显示edinger westphal核（EW）中Ucn mRNA和蛋白水平增加以及表达Ucn的细胞数量增加。这些CRF受体配体的水平反映了受体缺陷小鼠的状态。这些结果表明，CRFR 2在响应CRFR 1刺激HPA轴或焦虑时可能具有调节功能。
Corticotropin releasing factor (CRF) is a critical integrator of the hypothalamic-pituitary-adrenal (HPA) axis in response to stress. CRF and its related molecule urocortin (UCN) bind CRF receptor I (CRFR1) and CP.FR2 with distinct affinities. Mice deficient for CRFR1 or CRFR2 were generated in order to determine the physiological role of these receptors. While CRFR1-mutant mice show a depleted stress response and display anxiolytic-like behavior, CRFR2-mutant mice are hypersensitive to stress and display anxiogenic-like behavior. Both CRFR1- and CRFR2-mutant mice show normal basal feeding and weight gain, but CRFR2-mutant mice exhibit decreased food intake following a stress of food deprivation. While CRFR2-mutant mice display increased levels of CRF mRNA in the central nucleus of the amygdala. (cAmyg) but not in the paraventricular nucleus of the hypothalamus (PVN), the CRFR1-mutant mice express high levels of CRF in the PVN but normal levels in the cAmyg. CRFR2-mutant mice also display increased levels of Ucn mRNA and protein in the edinger westphal nucleus (EW) as well as an increased number of cells expressing Ucn. The levels of these CRF-receptor ligands reflect the state of the receptor-deficient mice. These results demonstrate a possible modulatory function of CRFR2 in response to CRFR1 stimulation of the HPA axis or anxiety.