Fast Feedback Inhibition of the HPA Axis by Glucocorticoids Is Mediated by Endocannabinoid Signaling
Fast Feedback Inhibition of the HPA Axis by Glucocorticoids Is Mediated by Endocannabinoid Signaling
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DOI：
10.1210/en.2010-0285
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发表时间：
2010-10-01
期刊：
影响因子：
4.8
通讯作者：
Herman, James P.
中科院分区：
文献类型：
--
作者：
Evanson, Nathan K.;Tasker, Jeffrey G.;Herman, James P.
糖皮质激素的分泌是为了响应激活下丘脑-垂体-肾上腺皮质 (HPA) 轴的刺激，并通过负反馈进行自我调节。人们认为快速发生的负反馈是通过非基因组机制发挥作用的。在这些研究中，我们研究了糖皮质激素对下丘脑室旁核 (PVN) 的直接作用对 HPA 轴应激反应的快速反馈抑制。将地塞米松或不透膜的地塞米松-BSA结合物局部输注到PVN中，以与细胞膜反馈作用一致的方式快速抑制约束诱导的ACTH和皮质酮释放。地塞米松快速反馈反应被大麻素 CB1 受体拮抗剂 AM-251 阻断，表明快速反馈需要局部释放内源性大麻素。下丘脑组织内源性大麻素 2-花生四烯酰甘油的含量因束缚应激而升高，这与内源性大麻素对反馈过程的作用一致。这些数据支持这样的假设：糖皮质激素诱导的 HPA 轴快速反馈抑制是由非基因组信号传导机制介导的，该机制涉及 PVN 水平的内源性大麻素信号传导。 （内分泌学151：4811-4819，2010）
Glucocorticoid hormones are secreted in response to stimuli that activate the hypothalamo-pituitary-adrenocortical (HPA) axis and self-regulate through negative feedback. Negative feedback that occurs on a rapid time scale is thought to act through nongenomic mechanisms. In these studies, we investigated fast feedback inhibition of HPA axis stress responses by direct glucocorticoid action at the paraventricular nucleus of the hypothalamus (PVN). Local infusion of dexamethasone or a membrane-impermeant dexamethasone-BSA conjugate into the PVN rapidly inhibits restraint-induced ACTH and corticosterone release in a manner consistent with feedback actions at the cell membrane. The dexamethasone fast feedback response is blocked by the cannabinoid CB1 receptor antagonist AM-251, suggesting that fast feedback requires local release of endocannabinoids. Hypothalamic tissue content of the endocannabinoid 2-arachidonoyl glycerol is elevated by restraint stress, consistent with endocannabinoid action on feedback processes. These data support the hypothesis that glucocorticoid-induced fast feedback inhibition of the HPA axis is mediated by a nongenomic signaling mechanism that involves endocannabinoid signaling at the level of the PVN. (Endocrinology 151: 4811-4819, 2010)