Suzuki H, Onaka T, Kasai M, Kawasaki M, Ohnishi H, Otsubo H, Saito T, Hashimoto H, Yokoyama T, Fujihara H, Dayanithi G, Murphy D, Nakamura T, Ueta Y
Department of Physiology, School of Medicine, University of Occupational and Environmental Health, Kitakyushu, Japan.
J Neuroendocrinol. 2009 Mar;21(3):183-90. doi: 10.1111/j.1365-2826.2009.01818.x.
Arginine vasopressin (AVP) and corticotrophin-releasing hormone (CRH) in the parvocellular neurosecretory cells of the paraventricular nucleus (PVN) play a major role in activating the hypothalamic-pituitary-adrenal axis, which is the main neuroendocrine response against the many kinds of stress. We examined the effects of chronic inflammatory/nociceptive stress on the expression of the AVP-enhanced green fluorescent protein (eGFP) fusion gene in the hypothalamus, using the adjuvant arthritis (AA) model. To induce AA, the AVP-eGFP rats were intracutaneously injected heat-killed Mycobacterium butyricum (1 mg/rat) in paraffin liquid at the base of their tails. We measured AVP, oxytocin and corticosterone levels in plasma and changes in eGFP and CRH mRNA in the hypothalamus during the time course of AA development. Then, we examined eGFP fluorescence in the PVN, the supraoptic nucleus (SON), median eminence (ME) and posterior pituitary gland (PP) when AA was established. The plasma concentrations of AVP, oxytocin and corticosterone were significantly increased on days 15 and 22 in AA rats, without affecting the plasma osmolality and sodium. Although CRH mRNA levels in the PVN were significantly decreased, eGFP mRNA levels in the PVN and the SON were significantly increased on days 15 and 22 in AA rats. The eGFP fluorescence in the SON, the PVN, internal and external layers of the ME and PP was apparently increased in AA compared to control rats. These results suggest that the increases in the concentrations of ACTH and corticosterone in AA rats are induced by hypothalamic AVP, based on data from AVP-eGFP transgenic rats.
室旁核（PVN）小细胞神经分泌细胞中的精氨酸加压素（AVP）和促肾上腺皮质激素释放激素（CRH）在激活下丘脑 - 垂体 - 肾上腺轴中起主要作用，该轴是针对多种应激的主要神经内分泌反应。我们使用佐剂性关节炎（AA）模型研究了慢性炎症/伤害性应激对下丘脑AVP增强型绿色荧光蛋白（eGFP）融合基因表达的影响。为诱导AA，给AVP - eGFP大鼠尾根部皮内注射石蜡液中热灭活的丁酸分枝杆菌（1mg/只大鼠）。我们在AA发展的时间进程中测量了血浆中AVP、催产素和皮质酮水平以及下丘脑eGFP和CRH mRNA的变化。然后，在AA形成后，我们检查了PVN、视上核（SON）、正中隆起（ME）和垂体后叶（PP）中的eGFP荧光。AA大鼠在第15天和第22天血浆中AVP、催产素和皮质酮浓度显著升高，而不影响血浆渗透压和钠。虽然PVN中CRH mRNA水平显著降低，但AA大鼠在第15天和第22天PVN和SON中的eGFP mRNA水平显著升高。与对照大鼠相比，AA大鼠SON、PVN、ME内外层和PP中的eGFP荧光明显增加。基于来自AVP - eGFP转基因大鼠的数据，这些结果表明AA大鼠中促肾上腺皮质激素和皮质酮浓度的增加是由下丘脑AVP诱导的。
