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首页> 外文期刊>Life sciences >The role of endogenous cannabinoids in the hypothalamo-pituitary-adrenal axis regulation: in vivo and in vitro studies in CB1 receptor knockout mice
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The role of endogenous cannabinoids in the hypothalamo-pituitary-adrenal axis regulation: in vivo and in vitro studies in CB1 receptor knockout mice

机译：内源性大麻素在下丘脑-垂体-肾上腺轴调节中的作用：CB1受体敲除小鼠的体内和体外研究

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Exogenous cannabinoids affect multiple hormonal systems including the hypothalamo-pituitary-adrenocortical (HPA) axis. These data suggest that endogenous cannabinoids are also involved in the HPA control; however, the mechanisms underlying this control are poorly understood. We assessed the role of endogenous cannabinoids in the regulation of the HPA-axis by studying CB1 receptor knockout (KO) and wild type (WT) mice. Basal and novelty stress-induced plasma levels of adrenocorticotropin (ACTH) and corticosterone were higher in CB1-KO than in WT mice. We investigated the involvement of the pituitary in the hormonal effects of CB1 gene disruption by studying the in vitro release of ACTH from anterior pituitary fragments using a perifusion system. Both the basal and corticotropin releasing hormone (CRH)-induced ACTH secretion were similar in CB1-KO and WT mice. The synthetic glucocorticoid, dexamethasone suppressed the CRH-induced ACTH secretion in both genotypes; thus, the negative feedback of ACTH secretion was not affected by CB1 gene disruption. The cannabinoid agonist, WIN 55,212-2 had no effects on basal and CRH-stimulated ACTH secretion by anterior pituitary slices. In our hands, the disruption of the CB1 gene lead to HPA axis hyperactivity, but the pituitary seems not to be involved in this effect. Our data are consistent with the assumption that endogenous cannabinoids inhibit the HPA-axis via centrally located CB1 receptors, however the understanding of the exact underlying mechanism needs further investigation. (C) 2004 Elsevier Inc. All rights reserved.
机译：外源性大麻素影响多种激素系统，包括下丘脑-垂体-肾上腺皮质（HPA）轴。这些数据表明内源性大麻素也参与了HPA的控制。但是，对该控制的基本机制了解甚少。我们通过研究CB1受体敲除（KO）和野生型（WT）小鼠，评估了内源性大麻素在HPA轴调节中的作用。基础和新奇应激诱导的血浆肾上腺皮质激素（ACTH）和皮质酮水平在CB1-KO中比在WT小鼠中更高。我们通过使用灌注融合系统研究垂体前叶碎片的体外ACTH释放，研究了垂体在CB1基因破坏的激素作用中的作用。在CB1-KO和WT小鼠中，基础释放激素和促肾上腺皮质激素释放激素（CRH）诱导的ACTH分泌均相似。合成的糖皮质激素地塞米松在两种基因型中均抑制了CRH诱导的ACTH分泌。因此，ACTH分泌的负反馈不受CB1基因破坏的影响。大麻素激动剂WIN 55,212-2对垂体前叶切片的基底和CRH刺激的ACTH分泌没有影响。在我们手中，CB1基因的破坏导致HPA轴功能亢进，但垂体似乎不参与这种作用。我们的数据与内源性大麻素通过位于中心的CB1受体抑制HPA轴的假设是一致的，但是对确切的潜在机制的理解需要进一步研究。 （C）2004 Elsevier Inc.保留所有权利。

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