Lack of Decrease in Hypothalamic and Hippocampal Glucocorticoid Receptor mRNA during Starvation

Lack of Decrease in Hypothalamic and Hippocampal Glucocorticoid Receptor mRNA during Starvation
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饥饿期间下丘脑和海马糖皮质激素受体 mRNA 缺乏减少

DOI:
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发表时间:
2001
期刊:
影响因子:
4.1
通讯作者:
Kozo Hashimoto
Kozo Hashimoto
中科院分区:
医学2区
文献类型:
--
作者:
S. Makino;T. Kaneda;M. Nishiyama;K. Asaba;Kozo Hashimoto

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我们在之前的一项研究中表明,在反复固定应激期间,高皮质酮水平会导致下丘脑室旁核(PVN)和海马中糖皮质激素受体(GR) mRNA的减少。GR的减少可能是糖皮质激素负反馈丢失或减少的原因,因此下丘脑-垂体-肾上腺皮质(HPA)轴的功能亢进在慢性应激期间持续存在。饥饿是一种应激状态,在这种状态下,中枢神经系统会产生对抗食物损失的反调节反应。我们探讨了饥饿对大鼠海马、PVN和垂体前叶(AP)中HPA轴、GR和矿糖皮质激素受体(MR) mrna的影响。大鼠连续饥饿4 d,早晨处死。饥饿大鼠血浆皮质酮水平高,而血浆促肾上腺皮质激素(ACTH)、促肾上腺素原黑素(POMC) mRNA和促肾上腺皮质激素1型释放激素(CRH)受体mRNA在饥饿大鼠中均未改变。在高皮质酮存在的情况下,饥饿导致PVN中CRH mRNA和1型CRH受体mRNA的减少。与此一致的是,尽管血浆皮质酮升高,但饥饿大鼠海马(CA1-2、CA3和齿状回)、PVN或AP中的GR mRNA并未出现任何变化。齿状回和AP区MR mRNA表达明显降低,而CA1-2、CA3和PVN区MR mRNA表达不明显。GR缺乏还原可能是机体在饥饿期间的反调节反应之一,它允许完整的糖皮质激素负反馈,从而导致PVN中厌食神经肽水平(即CRH)下降。结果还表明,海马和其他脑区域的GR mRNA并不仅仅受循环糖皮质激素的调节。中枢神经系统中GR mRNA调控的机制尚不清楚。
We have shown in a previous study that high corticosterone levels during repeated immobilization stress result in a reduction of glucocorticoid receptor (GR) mRNA in the hypothalamic paraventricular nucleus (PVN) and the hippocampus. The reduction of GR presumably accounts for loss of or decrease in glucocorticoid-negative feedback, and thus hyperfunction of the hypothalamic-pituitary-adrenocortical (HPA) axis persists during chronic stress. Starvation is a stress state in which the counterregulatory responses against the loss of food occur in the central nervous system. We explored the impact of starvation on the HPA axis, GR and mineralocorticoid receptor (MR) mRNAs in the hippocampus, the PVN, and the anterior pituitary (AP) of rats. Rats were starved for 4 days and sacrificed in the morning. Starved rats showed high levels of plasma corticosterone, whereas neither plasma corticotropin (ACTH), AP proopiomelanocortin (POMC) mRNA nor AP type-1 corticotropin-releasing hormone (CRH) receptor mRNA was altered in the starved rats. In the presence of high corticosterone, starvation resulted in a decrease in both CRH mRNA and type-1 CRH receptor mRNA in the PVN. Consistently, the starved rats did not show any changes in GR mRNA in the hippocampus (CA1-2, CA3, and dentate gyrus), the PVN or the AP despite the elevation of plasma corticosterone. A significant decrease in MR mRNA was seen in the dentate gyrus and the AP, but not in CA1–2, CA3 or PVN. The lack of reduction of GR may be one of the organism’s counterregulatory responses during starvation, which allows an intact glucocorticoid negative feedback, thereby resulting in decreased anorectic neuropeptide levels, namely CRH, in the PVN. The results also indicate that GR mRNA in the hippocampus and other brain regions is not solely regulated by circulating glucocorticoids. The mechanism underlying the regulation of GR mRNA in the central nervous system remains to be clarified.
DOI: 10.1159/000126839
发表时间: 1995-02-01
期刊: NEUROENDOCRINOLOGY
影响因子: 4.1
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影响因子: 11.2
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DOI: 10.1210/endo.133.6.8243338
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期刊: Endocrinology
影响因子: 4.8
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DOI: --
发表时间: 1995
期刊: The Journal of pharmacology and experimental therapeutics.
影响因子: --
作者:
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通讯作者: Bloom,FE
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DOI: 10.1210/mend.8.10.7854351
发表时间: 1994
期刊: Molecular endocrinology (Baltimore, Md.)
影响因子: --
作者:
Vig,E;Barrett,TJ;Vedeckis,WV
通讯作者: Vedeckis,WV