Urocortin 3 modulates the neuroendocrine stress response and is regulated in rat amygdala and hypothalamus by stress and glucocorticoids
Urocortin 3 modulates the neuroendocrine stress response and is regulated in rat amygdala and hypothalamus by stress and glucocorticoids
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DOI：
10.1210/en.2006-0545
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发表时间：
2006-10-01
期刊：
影响因子：
4.8
通讯作者：
Vale, Wylie
中科院分区：
文献类型：
--
作者：
Jamieson, Pauline M.;Li, Chien;Vale, Wylie
内源性促肾上腺皮质激素释放因子（CRF）2型受体（CRFR 2）选择性配体尿皮质素3在离散的皮质下脑区表达，纤维主要分布于下丘脑和边缘结构。下丘脑、外侧隔和内侧杏仁核（MEA）中主要尿皮质素3末端区域与CRFR 2之间的密切解剖学关联表明，它很好地调节了对压力的行为和激素反应。在基础条件下或束缚应激前，向雄性大鼠脑室内给予尿皮质素3，并测定循环ACTH、皮质酮、葡萄糖和胰岛素。Urocortin 3在基础条件下激活下丘脑-垂体-肾上腺轴，并增强ACTH对束缚应激的反应。两组中血糖升高和胰岛素与葡萄糖比值降低表明交感神经活性增加。尿皮质素3也增加了循环中的儿茶酚胺，为交感肾上腺髓质刺激提供了额外的证据。脑室内尿皮质素3增加加压素mRNA的表达在下丘脑室旁核的小细胞分裂，而CRF的表达是不变的，提供了一个可能的机制，尿皮质素3介导其行动。Urocortin 3 mRNA的表达进行了检查后，暴露于应力相关的范例。限制增加MEA的水平，有增加下丘脑穹窿周围区的表达的趋势，而出血和食物剥夺减少MEA的表达。肾上腺切除术显着增加表达在喙穹窿周围下丘脑区，高水平的皮质酮替代恢复到对照水平。尿皮质素3有可能影响应激反应的激素组分及其在应激后表达水平的变化的证据与内源性肽在调节应激反应中的潜在功能一致。
The endogenous corticotropin-releasing factor (CRF) type 2 receptor (CRFR2)-selective ligand urocortin 3 is expressed in discrete subcortical brain regions with fibers distributed mainly to hypothalamic and limbic structures. Close anatomical association between major urocortin 3 terminal fields and CRFR2 in hypothalamus, lateral septum, and medial amygdala ( MEA) suggest it is well placed to modulate behavioral and hormonal responses to stress. Urocortin 3 was administered intracerebroventricularly to male rats under basal conditions or before a restraint stress, and circulating ACTH, corticosterone, glucose, and insulin were measured. Urocortin 3 activated the hypothalamic-pituitary-adrenal axis under basal conditions and augmented ACTH responses to restraint stress. Elevated blood glucose with lowered insulin to glucose ratios in both groups suggested increased sympathetic activity. Circulating catecholamines were also increased by urocortin 3, providing additional evidence for sympathoadrenomedullary stimulation. Intracerebroventricular urocortin 3 increased vasopressin mRNA expression in the parvocellular division of the hypothalamic paraventricular nucleus, whereas CRF expression was unchanged, providing a possible mechanism by which urocortin 3 mediates its actions. Urocortin 3 mRNA expression was examined after exposure to stress-related paradigms. Restraint increased levels in MEA with a trend to increased expression in the rostral perifornical hypothalamic area, whereas hemorrhage and food deprivation decreased expression in MEA. Adrenalectomy markedly increased expression in the rostral perifornical hypothalamic area, and high-level corticosterone replacement restored this to control levels. The evidence that urocortin 3 has the potential to influence hormonal components of the stress response and the changes in its expression levels after stressors is consistent with a potential function for the endogenous peptide in modulating stress responses.