Lipopolysaccharide-induced oestrogen receptor regulation in the paraventricular hypothalamic nucleus of lewis and Fischer rats.
Lipopolysaccharide-induced oestrogen receptor regulation in the paraventricular hypothalamic nucleus of lewis and Fischer rats.
复制标题
刘易斯和费舍尔大鼠室旁下丘脑核中脂多糖诱导的雌激素受体调节。
DOI：
10.1046/j.1365-2826.2002.00841.x
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发表时间：
2002
影响因子：
3.2
通讯作者：
Sternberg,E
中科院分区：
文献类型：
--
作者：
Tonelli,L;Kramer,P;Webster,JI;Wray,S;Listwak,S;Sternberg,E
雌激素受体（ER）对神经分泌细胞和垂体细胞基因转录的调节已被认为是几种哺乳动物（包括人类）雌性下丘脑-垂体-肾上腺（HPA）轴反应增加的重要机制。近交雌性Fischer（F344/N）和刘易斯（LEW/N）大鼠具有相似的雌激素水平，尽管Fischer大鼠表现出高HPA轴反应和刘易斯大鼠低HPA轴反应。刘易斯大鼠HPA轴反应的钝化与其下丘脑促肾上腺皮质激素释放激素（CRH）表达的钝化有关。为了确定雌性刘易斯大鼠CRH表达缺陷是否与ER表达和调节缺陷相关，在基础条件下和免疫攻击后测定下丘脑室旁核（PVN）CRH和ER的转录水平。从对照组和脂多糖（LPS）处理的刘易斯和Fischer大鼠中获得显微切割的PVN，并通过半定量逆转录酶-聚合酶链反应测定CRH、ERα和β mRNA水平。此外，通过半定量Western印迹法测定ERα和β蛋白水平。对照组Fischer大鼠室旁核ERα和ER β mRNA及蛋白水平均显著高于对照组刘易斯大鼠。当CRH mRNA水平达到最大值时，Fischer大鼠的ERα和β mRNA及蛋白水平被LPS给药降低，但刘易斯大鼠的ERα和β mRNA及蛋白水平没有变化，这种效应与雌激素水平无关。这些数据表明，有缺陷的神经内分泌HPA轴反应与缺陷的ER表达和调节刘易斯PVN，尽管雌激素浓度。
Oestrogen receptor (ER) regulation of gene transcription in neurosecretory and pituitary cells has been proposed as an important mechanism for increased hypothalamic‐pituitary‐adrenal (HPA) axis responses in females of several mammalian species, including humans. Inbred female Fischer (F344/N) and Lewis (LEW/N) rats have similar oestrogen levels, although Fischer rats exhibit hyper‐ and Lewis rats hypo‐HPA axis responses. The blunted HPA axis response of Lewis rats has been associated with their blunted hypothalamic corticotropin releasing hormone (CRH) expression. To determine if the female CRH expression deficiency in Lewis rats is associated with defective ER expression and regulation, hypothalamic paraventricular nucleus (PVN) transcript levels of CRH and ER were determined under basal conditions and after immune challenge. Microdissected PVN were obtained from control and lipopolysaccharide (LPS) treated Lewis and Fischer rats and CRH, ERα and β mRNA levels were determined by semiquantitative reverse‐transcriptase‐polymerase chain reaction. In addition, ERα and β protein levels were determined by semiquantitative Western blots. ERα and β mRNA and protein levels in the PVN of control Fischer rats were significantly higher than in control Lewis rats. ERα and β mRNA and protein levels in Fischer rats were reduced by LPS administration at the time of maximal CRH mRNA levels but did not change in Lewis rats, an effect independent of oestrogen levels. These data indicate that defective neuroendocrine HPA axis responses are associated with defective ER expression and regulation in Lewis PVN despite oestrogen concentrations.