Sternberg E M, Glowa J R, Smith M A, Calogero A E, Listwak S J, Aksentijevich S, Chrousos G P, Wilder R L, Gold P W
Clinical Neuroendocrinology Branch, NIMH, ADAMHA, NIH, Bethesda, MD 20892.
Brain Res. 1992 Jan 20;570(1-2):54-60. doi: 10.1016/0006-8993(92)90563-o.
We have recently shown that susceptibility to streptococcal cell wall (SCW)-induced arthritis in Lewis (LEW/N) rats is related to a lack of glucocorticoid restraint of inflammation while the relative SCW arthritis resistance in histocompatible Fischer (F344/N) rats is related to their greater hypothalamic-pituitary-adrenal (HPA) axis response. The difference in pituitary-adrenal responsiveness results from decreased inflammatory mediator-induced hypothalamic corticotropin-releasing hormone (CRH) biosynthesis and secretion in LEW/N rats. Because CRH not only activates the pituitary-adrenal axis, but also is associated with behavioral responses that are adaptive during stressful situations, we wished to determine if the differential LEW/N and F344/N CRH responsiveness to inflammatory mediators could also be associated with differences in neuroendocrine and behavioral responses to physical and emotional stressors. In this study, LEW/N rats exhibited significant differences compared to F344/N rats, in plasma adrenocorticotropin hormone (ACTH) and corticosterone responses during exposure to an open field, swim stress, restraint or ether. Furthermore, hypothalamic paraventricular CRH mRNA expression was also significantly lower in LEW/N compared to F344/N rats after restraint. These differences in neuroendocrine responses were associated with differences in behavioral responses in LEW/N compared to F344/N rats in the open field. Outbred HSD rats, which have intermediate and overlapping arthritis susceptibility compared to LEW/N and F344/N rats, exhibited intermediate and overlapping plasma corticosterone and behavioral responses to stressful stimuli compared to the two inbred strains. These data suggest that the differences in CRH responses in these strains may contribute to the behavioral and neuroendocrine differences we have observed. Therefore these strains may provide a useful animal model for studying the relationship between behavior, neuroendocrine and inflammatory responses.
我们最近发现，Lewis（LEW/N）大鼠对链球菌细胞壁（SCW）诱导的关节炎的易感性与缺乏糖皮质激素对炎症的抑制有关，而组织相容性Fischer（F344/N）大鼠对SCW关节炎的相对抗性则与其更强的下丘脑-垂体-肾上腺（HPA）轴反应有关。垂体-肾上腺反应性的差异是由于LEW/N大鼠中炎症介质诱导的下丘脑促肾上腺皮质激素释放激素（CRH）生物合成和分泌减少所致。由于CRH不仅能激活垂体-肾上腺轴，还与应激情况下具有适应性的行为反应有关，我们希望确定LEW/N和F344/N对炎症介质的CRH反应差异是否也与对物理和情绪应激源的神经内分泌和行为反应差异有关。在本研究中，与F344/N大鼠相比，LEW/N大鼠在暴露于旷场、游泳应激、束缚或乙醚时，血浆促肾上腺皮质激素（ACTH）和皮质酮反应存在显著差异。此外，束缚后，LEW/N大鼠下丘脑室旁核CRH mRNA表达也显著低于F344/N大鼠。与F344/N大鼠相比，LEW/N大鼠在旷场中的这些神经内分泌反应差异与行为反应差异相关。与LEW/N和F344/N大鼠相比，具有中等和重叠关节炎易感性的远交HSD大鼠对应激刺激的血浆皮质酮和行为反应也呈现中等和重叠状态。这些数据表明，这些品系中CRH反应的差异可能导致了我们观察到的行为和神经内分泌差异。因此，这些品系可能为研究行为、神经内分泌和炎症反应之间的关系提供一个有用的动物模型。
