INFLUENCE OF 6-OHDA LESION OF CENTRAL NORADRENERGIC SYSTEMS ON CORTICOSTEROID RECEPTORS AND NEUROENDOCRINE RESPONSES TO STRESS
INFLUENCE OF 6-OHDA LESION OF CENTRAL NORADRENERGIC SYSTEMS ON CORTICOSTEROID RECEPTORS AND NEUROENDOCRINE RESPONSES TO STRESS
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DOI：
10.1016/0006-8993(90)91795-i
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发表时间：
1990-11-12
期刊：
影响因子：
2.9
通讯作者：
MORMEDE, P
中科院分区：
文献类型：
--
作者：
MACCARI, S;LEMOAL, M;MORMEDE, P
海马和下丘脑中的两种肾上腺皮质激素受体（I型或矿皮质激素和II型或糖皮质激素）介导皮质激素对各种脑功能的影响，包括对下丘脑-垂体-肾上腺（HPA）轴活性的负反馈控制。这些脑区也被去甲肾上腺素能终端密集支配，这些终端可能在HPA轴活性的调节和皮质类固醇的反馈作用中发挥作用。然而，缺乏皮质酮受体的去甲肾上腺素能控制的直接证据。本实验检测了6-羟多巴胺损伤小脑上足部去甲肾上腺素能上升通路对ⅰ型和ⅱ型皮质类固醇受体状态的影响。在术后3周切除24小时肾上腺的动物细胞质中评估[3H]皮质酮的结合。PCS病变引起海马I型皮质类固醇受体和下丘脑II型皮质类固醇受体的上调。这些受体的数量（Bmax）增加，但它们对皮质酮的亲和力（Kd）没有变化。此外，在功能研究中，我们测试了损伤对应激神经内分泌反应的影响。损伤大鼠的血浆皮质酮水平在基础条件下和对温和处理或暴露于足震的应激反应中都较低，表明HPA轴的活性降低。这些结果与最近的研究一致，表明HPA轴上的去甲肾上腺素能通路具有促进功能，并表明这种作用可能通过皮质类固醇受体的调节来介导。虽然基础循环儿茶酚胺水平未因损伤而改变，但去甲肾上腺素对足部休克应激的反应增加。这一结果与皮质类固醇对交感神经-肾上腺髓质系统的强直抑制一致。这些数据进一步证明了儿茶酚胺能系统与皮质类固醇之间的密切关系。
Two types of receptor for adrenocortical hormones (type I or mineralocorticoid and type II or glucocorticoid) in the hippocampus and hypothalamus mediate the effects of corticosteroids on various brain functions including the negative feedback control of hypothalamo-pituitary-adrenal (HPA) axis activity. These brain regions are also densely innervated by noradrenergic terminals which may play a role in the regulation of HPA axis activity and the feedback action of corticosteroids. However, direct evidence for a noradrenergic control of corticosterone receptors is lacking. The present experiments tested the effects of 6-hydroxydopamine lesion of noradrenergic ascending pathways at the level of the pedunculus cerebellaris superior (PCS) on the status of type I and type II corticosteroid receptors. Binding of [3H]corticosterone was evaluated in cytosolic fractions of 24-h adrenalectomized animals 3 weeks after surgery. The PCS lesion produced an up-regulation of type I corticosteroid receptors in the hippocampus and of the type II receptor in the hypothalamus. The number of these receptors (Bmax) increased without any change in their affinity for corticosterone (Kd). Furthermore, in a functional study, we tested the effects of the lesion on the neuroendocrine responses to stress. Plasma corticosterone levels were lower in lesioned rats both under basal conditions and in response to the stress of gentle handling or exposure to footshock, indicating reduced activity of the HPA axis. These results are in line with recent studies indicating a facilitatory function or noradrenergic pathways on the HPA axis and suggest that this action could be mediated via a modulation of corticosteroid receptors. Although basal circulating catecholamine levels were not altered by the lesion, the noradrenaline response to footshock stress was increased. This result is consistent with the demonstrated tonic inhibition of the sympatho-adrenomedullary system by corticosteroid. These data provide further evidence for the close relationship between catecholaminergic systems and corticosteroids.