Makino S, Gold P W, Schulkin J
Behavioral Neuroscience Unit, National Institute of Mental Health, Bethesda, MD 20892.
Brain Res. 1994 Mar 21;640(1-2):105-12. doi: 10.1016/0006-8993(94)91862-7.
Using in situ hybridization histochemistry, we report differential expression of corticotropin-releasing hormone (CRH) mRNA in the central nucleus of the amygdala (CEA) and the parvocellular region of the paraventricular nucleus of the hypothalamus (PVN) following systemic treatment with corticosterone (CORT) in adrenally-intact rats. Both injection of low (1 mg/kg/day) and high (5 mg/day) CORT reduced CRH mRNA expression in the PVN in a dose-dependent manner, although it returned to normal at the low dose by 14 days. By contrast, the high dose of CORT increased CRH mRNA transiently in the CEA at 4 days, although the low dose of CORT decreased it at 14 days. In a second experiment, we implanted a slowly-releasing CORT pellet for 2 weeks (200 mg, 60 day release) subcutaneously. This treatment produced an elevation of CRH mRNA in the CEA both at 1 and 2 weeks, whereas CRH mRNA in the PVN was decreased to a large extent as seen in the high CORT group of the first experiment. These results suggest that glucocorticoids can facilitate CRH mRNA expression in the CEA, a site implicated in anxiety and fear, while restraining the hypothalamic-pituitary-adrenal axis as indicated by the reduction in CRH mRNA in the PVN.
运用原位杂交组织化学技术,我们报告了在肾上腺功能正常的大鼠中,经皮质酮(CORT)全身治疗后,促肾上腺皮质激素释放激素(CRH)mRNA在杏仁核中央核(CEA)和下丘脑室旁核小细胞区(PVN)中的差异表达。低剂量(1mg/kg/天)和高剂量(5mg/天)的CORT注射均以剂量依赖方式降低了PVN中的CRH mRNA表达,不过低剂量时在14天时恢复正常。相比之下,高剂量的CORT在第4天时使CEA中的CRH mRNA短暂增加,而低剂量的CORT在第14天时使其降低。在第二个实验中,我们皮下植入了一个缓慢释放的CORT丸剂两周(200mg,60天释放)。这种治疗在第1周和第2周时均使CEA中的CRH mRNA升高,而PVN中的CRH mRNA则如第一个实验中的高CORT组那样大幅降低。这些结果表明,糖皮质激素可促进CEA中CRH mRNA的表达,CEA是一个与焦虑和恐惧有关的部位,同时如PVN中CRH mRNA的减少所示,抑制下丘脑 - 垂体 - 肾上腺轴。