Aguilera G, Jessop D S, Harbuz M S, Kiss A, Lightman S L
Section on Endocrine Physiology, National Institute of Child Health and Human Development, NIH, Bethesda, Maryland 20892, USA.
J Endocrinol. 1997 May;153(2):185-91. doi: 10.1677/joe.0.1530185.
The expression of corticotropin releasing hormone (CRH) in the hypothalamic paraventricular nucleus (PVN) and CRH receptor mRNA in the PVN and anterior pituitary was studied during development of adjuvant-induced arthritis in Piebald-Viral-Glaxo rats, using in situ hybridization techniques. As previously shown with i.p. hypertonic saline injection, basal and immobilization stress-stimulated CRH mRNA levels in the PVN were significantly lower than in controls 14 days after adjuvant injection. However, 7 days after injection, preceding the onset of inflammation, the increase of CRH mRNA following immobilization was significantly higher than in control rats. In contrast to other chronic stress paradigms, inflammation stress failed to induce type-1 CRH receptor (CRH-R1) mRNA in the PVN, either at 7 days, or at 14 days after adjuvant injection, when inflammation is present. The ability of acute immobilization to induce CRH-R1 mRNA in the PVN was not affected 14 days after adjuvant injection but parallel to the CRH peptide mRNA response it was markedly potentiated at 7 days. Pro-opiomelanocorpin (POMC) mRNA levels in the anterior pituitary increased significantly 14 days after adjuvant injection, and they were unaffected by 1 h immobilization. While CRH binding in the pituitary decreased significantly 14 days after adjuvant injection, CRH-R1 mRNA was unchanged. This study shows biphasic hypothalamic responses to acute stress during development of adjuvant-induced arthritis, with enhanced CRH peptide and CRH-R1 mRNAs responses at 7 days, preceding the onset of inflammation, and blunted CRH mRNA responses at 14 days at the height of the inflammatory response. The lack of CRH receptor expression in the PVN in this model of chronic inflammation stress associated to low hypothalamic CRH peptide levels supports the view that positive feedback regulation by CRH is necessary to maintain enhanced CRH expression during chronic stress.
采用原位杂交技术，研究了斑驳病毒 - 葛兰素大鼠佐剂性关节炎发展过程中，下丘脑室旁核（PVN）中促肾上腺皮质激素释放激素（CRH）的表达以及PVN和垂体前叶中CRH受体mRNA的表达情况。如先前腹腔注射高渗盐水所示，佐剂注射14天后，PVN中基础和固定应激刺激的CRH mRNA水平显著低于对照组。然而，注射后7天，在炎症发作之前，固定后CRH mRNA的增加显著高于对照大鼠。与其他慢性应激模式不同，在佐剂注射后7天或14天炎症存在时，炎症应激未能诱导PVN中的1型CRH受体（CRH-R1）mRNA。佐剂注射14天后，急性固定诱导PVN中CRH-R1 mRNA的能力未受影响，但与CRH肽mRNA反应平行，在7天时明显增强。佐剂注射14天后，垂体前叶中阿黑皮素原（POMC）mRNA水平显著增加，且不受1小时固定的影响。虽然佐剂注射14天后垂体中的CRH结合显著降低，但CRH-R1 mRNA未发生变化。本研究表明，在佐剂性关节炎发展过程中，下丘脑对急性应激有双相反应，在炎症发作前7天，CRH肽和CRH-R1 mRNA反应增强，而在炎症反应高峰期14天，CRH mRNA反应减弱。在这种与下丘脑CRH肽水平低相关的慢性炎症应激模型中，PVN中缺乏CRH受体表达支持了这样一种观点，即CRH的正反馈调节对于在慢性应激期间维持增强的CRH表达是必要的。
