The Neuroscience Graduate Program and Department of Biological Sciences, USC Dornsife College of Letters, Arts, and Sciences, University of Southern California, Los Angeles, CA 90089-2520, USA.
J Neuroendocrinol. 2012 Dec;24(12):1517-26. doi: 10.1111/j.1365-2826.2012.02363.x.
Corticotrophin-releasing hormone (CRH) neuroendocrine neurones in the paraventricular nucleus of the hypothalamus (PVH) drive adrenocorticotrophic hormone (ACTH) and thereby glucocorticoid release from pituitary corticotrophs and the adrenal cortex, respectively. Glucocorticoids suppress the ability of neuroendocrine corticotrophin-releasing hormone (CRH) neurones to synthesise and release ACTH secretogogues. Despite the importance of glucocorticoids as regulatory signals to CRH neurones in the extended time domain, how and where they act in this capacity is still not fully understood. Ascending catecholamine projections encode important cardiovascular, metabolic and other visceral information to the rat PVH and surrounding hypothalamus. These afferents have previously been implicated as targets for glucocorticoid action, including a role in the feedback regulation of PVH neuroendocrine neurones. To determine the contribution of these neurones to the long-term actions of corticosterone on CRH and vasopressin (AVP) gene expression in the PVH, we used an immunocytotoxin (a conjugate of the cytotoxin saporin and an antibody against dopamine-β-hydroxylase) that specifically ablates adrenergic and noradrenergic neurones. Lesions were administered to intact animals and to adrenalectomised animals with either no corticosterone or corticosterone replacement that provided levels above those required to normalise Crh expression. The ability of elevated levels of corticosterone to suppress Crh expression was abolished in animals lacking catecholaminergic innervation of the PVH. No effect was seen in the absence of corticosterone or in animals with intact adrenals. Furthermore, Avp expression, which is increased in CRH neurones following adrenalectomy, was suppressed in adrenalectomised catecholaminergic-lesioned animals. Interactions between corticosterone and catecholaminergic projections to the hypothalamus therefore make significant contributions to the regulation of Crh and Avp expression. However, the importance of catecholamine inputs is only apparent when circulating corticosterone concentrations are maintained either below or above those required to maintain the activity of the hypothalamic-pituitary-adrenal axis that is seen in intact animals.
下丘脑室旁核（PVH）中的促肾上腺皮质激素释放激素（CRH）神经内分泌神经元分别驱动促肾上腺皮质激素（ACTH）和皮质激素从垂体促皮质素细胞和肾上腺皮质释放。糖皮质激素抑制神经内分泌促肾上腺皮质激素释放激素（CRH）神经元合成和释放 ACTH 分泌剂的能力。尽管糖皮质激素作为调节信号对 CRH 神经元在扩展的时间域中非常重要，但它们在这种能力中的作用方式和位置仍不完全清楚。上升的儿茶酚胺投射将重要的心血管、代谢和其他内脏信息编码到大鼠 PVH 和周围下丘脑。这些传入纤维以前被认为是糖皮质激素作用的靶点，包括在 PVH 神经内分泌神经元的反馈调节中的作用。为了确定这些神经元对皮质酮对 PVH 中 CRH 和血管加压素（AVP）基因表达的长期作用的贡献，我们使用了一种免疫细胞毒素（细胞毒素相思豆毒素和抗多巴胺-β-羟化酶抗体的缀合物），该毒素特异性破坏去甲肾上腺素能和肾上腺素能神经元。在完整动物和去肾上腺动物中进行了损伤，去肾上腺动物没有皮质酮或皮质酮替代物，提供了高于使 Crh 表达正常化所需的水平。在缺乏 PVH 儿茶酚胺神经支配的动物中，升高的皮质酮水平抑制 Crh 表达的能力被消除。在没有皮质酮或在具有完整肾上腺的动物中未观察到这种作用。此外，在去肾上腺损伤的儿茶酚胺神经损伤动物中，AVP 表达在 CRH 神经元中增加被抑制。因此，皮质酮和下丘脑儿茶酚胺投射之间的相互作用对 Crh 和 Avp 表达的调节有重要贡献。然而，只有当循环皮质酮浓度保持在低于或高于维持完整动物中所见的下丘脑-垂体-肾上腺轴活性所需的水平时，儿茶酚胺输入的重要性才显现出来。
