Mechanisms Underlying the Increased Plasma ACTH Levels in Chronic Psychosocially Stressed Male Mice
Mechanisms Underlying the Increased Plasma ACTH Levels in Chronic Psychosocially Stressed Male Mice
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DOI：
10.1371/journal.pone.0084161
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发表时间：
2013-12-23
期刊：
影响因子：
3.7
通讯作者：
Reber, Stefan O.
中科院分区：
文献类型：
--
作者：
Fuechsl, Andrea M.;Langgartner, Dominik;Reber, Stefan O.
暴露于慢性从属群体住房（CSC，19天），慢性心理社会应激的一个既定的范例，小鼠显示不受影响的基础早晨血浆皮质酮（CORT）浓度，尽管扩大肾上腺和增加的CORT反应急性异型应激。在本研究中，我们调查的机制，这些现象在垂体的水平。我们发现，无论是基础和急性应激诱导（强迫游泳（FS），6分钟）CSC中血浆促肾上腺皮质激素（ACTH）浓度、垂体总细胞和促肾上腺皮质激素细胞数量以及垂体盐皮质激素受体和FK 506结合蛋白51的相对蛋白表达增加与单独饲养的对照（SHC）小鼠相比，促肾上腺皮质激素释放激素（CRH）受体1（CRH-R1）和糖皮质激素受体蛋白表达下调。相对垂体前阿黑皮素和精氨酸加压素（AVP）受体1b（AVPR-1b）蛋白表达，FS（6分钟）诱导的ACTH分泌地塞米松阻断小鼠，和AVP阳性的大细胞和小细胞神经元的数量在下丘脑室旁核（PVN）不受CSC。总之，本研究的数据表明，19天的CSC导致垂体功能亢进，在基础和急性异型应激条件下。尽管进一步的研究必须对此进行详细评估，但CSC后垂体促肾上腺皮质激素细胞数量的增加以及未受影响的相对垂体AVPR-1b和CRH-R1蛋白表达的减少表明，垂体超驱动是由新形成的促肾上腺皮质激素细胞介导的，这些促肾上腺皮质激素细胞对AVP比CRH更敏感。此外，我们的数据表明，PVN AVP和负反馈抑制的变化似乎没有发挥重要作用，垂体功能亢进CSC后。
Mice exposed to chronic subordinate colony housing (CSC, 19 days), an established paradigm for chronic psychosocial stress, show unaffected basal morning plasma corticosterone (CORT) concentrations, despite enlarged adrenal glands and an increased CORT response to an acute heterotypic stressor. In the present study we investigate the mechanisms underlying these phenomena at the level of the pituitary. We show that both basal and acute stressor-induced (forced swim (FS), 6 min) plasma adrenocorticotropic hormone (ACTH) concentrations, the number of total and corticotroph pituitary cells, and relative protein expression of pituitary mineralocorticoid receptor and FK506-binding protein 51 was increased in CSC compared with single-housed control (SHC) mice, while relative corticotropin releasing hormone (CRH) receptor 1 (CRH-R1) and glucocorticoid receptor protein expression was down-regulated. Relative pituitary pro-opiomelanocortin and arginine vasopressin (AVP) receptor 1b (AVPR-1b) protein expression, FS (6 min)-induced ACTH secretion in dexamethasone-blocked mice, and the number of AVP positive magnocellular and parvocellular neurons in the paraventricular hypothalamic nucleus (PVN) was unaffected following CSC. Taken together, the data of the present study indicate that 19 days of CSC result in pituitary hyperactivity, under both basal and acute heterotypic stress conditions. Although further studies have to assess this in detail, an increased number of pituitary corticotrophs together with unaffected relative pituitary AVPR-1b and decreased CRH-R1 protein expression following CSC suggests that pituitary hyperdrive is mediated by newly formed corticotrophs that are more sensitive to AVP than CRH. Moreover, our data indicate that changes in PVN AVP and negative feedback inhibition seem not to play a major role in pituitary hyperactivity following CSC.