Zelazowski P, Patchev V K, Zelazowska E B, Chrousos G P, Gold P W, Sternberg E M
National Institute of Mental Health, National Institutes of Health, Bethesda, MD 20892.
Brain Res. 1993 Dec 17;631(1):22-6. doi: 10.1016/0006-8993(93)91181-q.
The susceptibility of Lewis rats is related to blunted hypothalamic-pituitary-adrenal (HPA) axis responsiveness to a variety of inflammatory and neuroendocrine stimuli. In contrast resistance to inflammatory disease of histocompatible Fischer rats is associated with their intact HPA axis responses to the same stimuli. We have examined the contribution of IL-1 beta to in vitro corticotropin-releasing hormone (CRH) and arginine vasopressin (AVP) release from hypothalamic explants derived from LEW/N and F344/N rats. The same animal model has been used to investigate the regulatory effect of alpha MSH, an immunosuppressive neurohormone, on IL-1 beta stimulated CRH and AVP secretion. CRH basal release in both strains was similar. However, LEW/N hypothalamic AVP basal secretion was significantly elevated. CRH relative response of LEW/N hypothalamic explants to IL-1 beta stimulation was lower compared to Fischer, which is consistent with their hyporesponsiveness to inflammatory mediators. AVP secretion however, was significantly decreased in hypothalamic explants from both strains after 40 min exposure to IL-1 beta. alpha MSH suppressed basal CRH and AVP release in both LEW/N and F344/N rats and prevented IL-1 beta stimulated CRH secretion in these strains. AVP was further diminished in F344/N explants following incubation with alpha MSH + IL-1 beta, while LEW/N level was significantly elevated. However, AVP levels remained significantly below baseline in explants from both strains after final incubation with IL-1 beta. Although our findings indicate a modulatory action of alpha MSH in HPA axis regulation in vitro, the physiological importance of this phenomenon in Lewis and Fischer rats requires further investigation.
刘易斯大鼠的易感性与下丘脑 - 垂体 - 肾上腺（HPA）轴对多种炎症和神经内分泌刺激的反应迟钝有关。相比之下，组织相容性费希尔大鼠对炎症性疾病的抵抗力与其对相同刺激的完整HPA轴反应相关。我们研究了白细胞介素 - 1β（IL - 1β）对源自LEW/N和F344/N大鼠的下丘脑外植体中促肾上腺皮质激素释放激素（CRH）和精氨酸加压素（AVP）体外释放的作用。相同的动物模型已被用于研究免疫抑制神经激素α - 促黑素（αMSH）对IL - 1β刺激的CRH和AVP分泌的调节作用。两种品系的CRH基础释放相似。然而，LEW/N下丘脑AVP基础分泌显著升高。与费希尔大鼠相比，LEW/N下丘脑外植体对IL - 1β刺激的CRH相对反应较低，这与其对炎症介质的低反应性一致。然而，在暴露于IL - 1β 40分钟后，两种品系的下丘脑外植体中AVP分泌均显著减少。αMSH抑制了LEW/N和F344/N大鼠的基础CRH和AVP释放，并阻止了这些品系中IL - 1β刺激的CRH分泌。在与αMSH + IL - 1β孵育后，F344/N外植体中的AVP进一步减少，而LEW/N水平显著升高。然而，在与IL - 1β最终孵育后，两种品系外植体中的AVP水平仍显著低于基线。尽管我们的研究结果表明αMSH在体外HPA轴调节中具有调节作用，但这种现象在刘易斯大鼠和费希尔大鼠中的生理重要性需要进一步研究。
