A study on the regulatory mechanism of the hypothalamo-pituitary-adrenal axis

下丘脑-垂体-肾上腺轴调节机制的研究

基本信息

批准号：
08671127
负责人：
WATANOBE Hajime
金额：
$ 1.47万
依托单位：
HIROSAKI UNIVERSITY
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
1996
资助国家：
日本
起止时间：
1996 至 1997
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-08671127/
关键词：
Cytokine ACTH Lipopolysaccharide Prostaglandin Indomethacin CRH

项目摘要

1.It is known that systemic administration of lipopolysaccharide (LPS) stimulates the synthesis and secretion of various proinflammatory cytokines in both the general circulation and the brain. Thus, the relative contribution of peripheral and central cytokines to the activation of the corticotropin-releasing hormone (CRH) -adrenocorticotropin (ACTH) system is still poorly understood. In the present research project, this principal investigator attempted to examine this unresolved issue in more details. The results I obtained suggested that tumor necrosis factor (TNF) -alpha in the general circulation may play the most important role in triggering the early, peak phase of ACTH secretion after systemic LPS treatment in the rat.2.It has been repeatedly reported that indomethacin suppress the ACTH response to interleukin (IL) -1beta in the rat. Although this finding was construed as suggesting a stimulatory role of prostaglandins in mediating the hormonal response, a group of investigators have reported that this may not be the case. In the present study, this principal investigator attempted to clarify this issue, and found that the suppression by indomethacin of the IL-1beta-induced ACTH response is mediated by indomethacin's inherent pharmacological activity, i.e.the suppression of prostaglandin production.3.Utilizing IL-1 receptor antagonist which blocks the biological activity of IL-1, this proncipal investigator examined the involvement of brain IL-1 in mediating the ACTH response to intravenous or intracerebroventricular administration of LPS in the rat. Implications deriving from this study were that IL-1 in the brain may play an important role in mediating the ACTH secretion after intracerebroventricular, but not intravenous, administration of LPS in the rat.

1.众所周知，脂多糖（LPS）的全身施用会刺激一般循环和大脑中各种促炎细胞因子的合成和分泌。因此，周围和中央细胞因子对皮质激素释放激素（CRH） - 肾上腺皮质激素（ACTH）系统激活的相对贡献仍然很少了解。在本研究项目中，这位首席研究员试图在更多细节中检查这个尚未解决的问题。我获得的结果表明，一般循环中的肿瘤坏死因子（TNF） - α-可能在触发大鼠全身性LPS治疗后触发ACTH的早期，ACTH分泌的早期，峰值阶段。尽管这一发现被解释为表明前列腺素在介导荷尔蒙反应中的刺激作用，但一组研究人员报告说，情况并非如此。 In the present study, this principal investigator attempted to clarify this issue, and found that the suppression by indomethacin of the IL-1beta-induced ACTH response is mediated by indomethacin's inherent pharmacological activity, i.e.the suppression of prostaglandin production.3.Utilizing IL-1 receptor antagonist which blocks the biological activity of IL-1, this proncipal investigator examined the involvement of brain IL-1 in介导大鼠静脉内或脑室脑室室内给药的ACTH反应。这项研究的含义是，大脑中的IL-1在介导脑室脑室分泌（但不是静脉内）LPS在大鼠中的介导ACTH分泌方面可能起重要作用。