Estrogen-related receptor β deficiency alters body composition and response to restraint stress.
Estrogen-related receptor β deficiency alters body composition and response to restraint stress.
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DOI：
10.1186/1472-6793-13-10
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发表时间：
2013-09-22
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影响因子：
--
通讯作者：
Blackshaw S
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文献类型：
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作者：
Byerly MS;Swanson RD;Wong GW;Blackshaw S
雌激素相关受体（ERRs）是表达于代谢活性组织中的孤儿核激素受体，并调节许多稳态过程。雌激素受体不与雌激素配体结合，但它们能够与嵌入雌激素受体应答元件（ERRE）中的雌激素应答元件（ERE）结合以调节基因的转录。先前的研究表明，缺乏Errβ的成年小鼠的代谢和饮食模式发生了改变。为了进一步了解Errβ的生物学作用，我们表征了Errβ的一个或两个等位基因缺陷的小鼠的应激反应。Sox 2-Cre：Errβ小鼠在发育胚胎的所有组织中都缺乏Errβ表达。Sox 2-Cre：Errβ+/lox杂合子肥胖，下丘脑弓状核Npy和Agrp基因表达增加，应激时分泌更多的皮质酮。相反，Sox 2-Cre：Errβlox/lox纯合子是精瘦的，尽管Npy和Agrp基因表达增加，但在应激时没有分泌更多的皮质酮。用Errβ和Errγ激动剂DY 131处理的Sox 2-Cre：Errβ+/lox和Sox 2-Cre：Errβlox/lox小鼠显示下丘脑室旁核中促肾上腺皮质激素释放激素（Crh）表达增加，但皮质酮水平不受影响。Nes-Cre：Errβlox/lox小鼠在神经系统中选择性缺乏Errβ表达，在声惊吓反应试验期间也表现出应激反应升高，Crh和促肾上腺皮质激素释放激素受体2（Crhr 2）的表达降低。Errβ的缺失影响小鼠的身体组成、神经肽水平、应激激素和中枢调节的惊吓反应。这些结果表明，Errβ改变下丘脑-垂体-肾上腺皮质轴的功能，并表明Errβ在调节应激反应中的作用。
Estrogen-related receptors (ERRs) are orphan nuclear hormone receptors expressed in metabolically active tissues and modulate numerous homeostatic processes. ERRs do not bind the ligand estrogen, but they are able to bind the estrogen response element (ERE) embedded within the ERR response elements (ERREs) to regulate transcription of genes. Previous work has demonstrated that adult mice lacking Errβ have altered metabolism and meal patterns. To further understand the biological role of Errβ, we characterized the stress response of mice deficient for one or both alleles of Errβ. Sox2-Cre:Errβ mice lack Errβ expression in all tissues of the developing embryo. Sox2-Cre:Errβ+/lox heterozygotes were obese, had increased Npy and Agrp gene expression in the arcuate nucleus of the hypothalamus, and secreted more corticosterone in response to stress. In contrast, Sox2-Cre:Errβlox/lox homozygotes were lean and, despite increased Npy and Agrp gene expression, did not secrete more corticosterone in response to stress. Sox2-Cre:Errβ+/lox and Sox2-Cre:Errβlox/lox mice treated with the Errβ and Errγ agonist DY131 demonstrated increased corticotropin-releasing hormone (Crh) expression in the paraventricular nucleus of the hypothalamus, although corticosterone levels were not affected. Nes-Cre:Errβlox/lox mice, which selectively lack Errβ expression in the nervous system, also demonstrated elevated stress response during an acoustic startle response test and decreased expression of both Crh and corticotropin-releasing hormone receptor 2 (Crhr2). Loss of Errβ affects body composition, neuropeptide levels, stress hormones, and centrally-modulated startle responses of mice. These results indicate that Errβ alters the function of the hypothalamic-pituitary-adrenocortical axis and indicates a role for Errβ in regulating stress response.