Aluru Neelakanteswar, Jorgensen Even H, Maule Alec G, Vijayan Mathilakath M
Dept. of Biology, Univ. of Waterloo, Waterloo, Ontario, Canada.
Am J Physiol Regul Integr Comp Physiol. 2004 Oct;287(4):R787-93. doi: 10.1152/ajpregu.00091.2004. Epub 2004 Jun 17.
We examined whether brain glucocorticoid receptor (GR) modulation by polychlorinated biphenyls (PCBs) was involved in the abnormal cortisol response to stress seen in anadromous Arctic charr (Salvelinus alpinus). Fish treated with Aroclor 1254 (0, 1, 10, and 100 mg/kg body mass) were maintained for 5 mo without feeding in the winter to mimic their seasonal fasting cycle, whereas a fed group with 0 and 100 mg/kg Aroclor was maintained for comparison. Fasting elevated plasma cortisol levels and brain GR content but depressed heat shock protein 90 (hsp90) and interrenal cortisol production capacity. Exposure of fasted fish to Aroclor 1254 resulted in a dose-dependent increase in brain total PCB content. This accumulation in fish with high PCB dose was threefold higher in fasted fish compared with fed fish. PCBs depressed plasma cortisol levels but did not affect in vitro interrenal cortisol production capacity in fasted charr. At high PCB dose, the brain GR content was significantly lower in the fasted fish and this corresponded with a lower brain hsp70 and hsp90 content. The elevation of plasma cortisol levels and upregulation of brain GR content may be an important adaptation to extended fasting in anadromous Arctic charr, and this response was disrupted by PCBs. Taken together, the hypothalamus-pituitary-interrenal axis is a target for PCB impact during winter emaciation in anadromous Arctic charr.
我们研究了多氯联苯(PCBs)对大脑糖皮质激素受体(GR)的调节是否与溯河洄游型北极红点鲑(Salvelinus alpinus)应激时异常的皮质醇反应有关。用Aroclor 1254(0、1、10和100 mg/kg体重)处理的鱼在冬季不喂食维持5个月,以模拟它们的季节性禁食周期,而喂食了0和100 mg/kg Aroclor的对照组用于比较。禁食会提高血浆皮质醇水平和大脑GR含量,但会降低热休克蛋白90(hsp90)和肾间皮质醇的生成能力。将禁食的鱼暴露于Aroclor 1254会导致大脑总PCB含量呈剂量依赖性增加。高PCB剂量组鱼体内的这种积累量在禁食鱼中比喂食鱼高三倍。多氯联苯会降低血浆皮质醇水平,但不影响禁食红点鲑的体外肾间皮质醇生成能力。在高PCB剂量下,禁食鱼的大脑GR含量显著降低,这与较低的大脑hsp70和hsp90含量相对应。血浆皮质醇水平的升高和大脑GR含量的上调可能是溯河洄游型北极红点鲑对长期禁食的一种重要适应,而这种反应被多氯联苯破坏。综上所述,下丘脑 - 垂体 - 肾间轴是多氯联苯在溯河洄游型北极红点鲑冬季消瘦期间产生影响的一个靶点。