Aksentijevich S, Whitfield H J, Young W S, Wilder R L, Chrousos G P, Gold P W, Sternberg E M
Arthritis and Rheumatism Branch, NIAMS, Bethesda, MD 20892.
Brain Res Dev Brain Res. 1992 Jan 17;65(1):115-8. doi: 10.1016/0165-3806(92)90014-n.
Susceptibility to streptococcal cell wall (SCW)-induced arthritis in 4- to 6-week-old Lewis (LEW/N) rats is associated with blunted glucocorticoid production secondary to a profound defect in inflammatory mediator-induced hypothalamic corticotropin-releasing hormone (CRH) biosynthesis and secretion. The relative SCW arthritis resistance in histocompatible Fischer (F344/N) rats, on the other hand, is associated with robust hypothalamic-pituitary-adrenal (HPA) axis responses to inflammatory mediators. In this study, we investigated HPA axis responses to SCW during the postnatal developmental period in LEW/N and F344/N rats. We found that SCW-induced plasma corticosterone (CORT) responses do not significantly increase during development in LEW/N, while such responses clearly appear at postnatal day 14 in F344/N and outbred Harlan-Sprague-Dawley (HSD) rats. Additionally, LEW/N rats fail to exhibit the normal ontogenic increase in CRH mRNA levels in the paraventricular nucleus (PVN), whereas their SCW-induced PVN CRH mRNA responses are blunted compared to F344/N at postnatal day 14. Taken together, these results suggest that LEW/N rats fail to emerge completely from their stress hyporesponsive period. This may account for the lack of stress responsiveness in young adult LEW/N rats, and consequently, for their susceptibility to SCW-induced arthritis and other inflammatory diseases.
4至6周龄的Lewis（LEW/N）大鼠对链球菌细胞壁（SCW）诱导的关节炎易感，这与炎症介质诱导的下丘脑促肾上腺皮质激素释放激素（CRH）生物合成和分泌严重缺陷继发的糖皮质激素分泌减弱有关。另一方面，组织相容性Fischer（F344/N）大鼠对SCW关节炎具有相对抗性，这与下丘脑-垂体-肾上腺（HPA）轴对炎症介质的强烈反应有关。在本研究中，我们调查了LEW/N和F344/N大鼠出生后发育期间HPA轴对SCW的反应。我们发现，SCW诱导的血浆皮质酮（CORT）反应在LEW/N大鼠发育过程中没有显著增加，而在F344/N和远交Harlan-Sprague-Dawley（HSD）大鼠中，这种反应在出生后第14天明显出现。此外，LEW/N大鼠室旁核（PVN）中CRH mRNA水平未能呈现正常的个体发育性增加，而在出生后第14天，它们的SCW诱导的PVN CRH mRNA反应与F344/N相比减弱。综上所述，这些结果表明LEW/N大鼠未能完全从其应激低反应期恢复。这可能解释了年轻成年LEW/N大鼠缺乏应激反应性，进而导致它们对SCW诱导的关节炎和其他炎症性疾病易感。
