Stress Response of Prolactin-Releasing Peptide Knockout Mice as to Glucocorticoid Secretion
Stress Response of Prolactin-Releasing Peptide Knockout Mice as to Glucocorticoid Secretion
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DOI：
10.1111/j.1365-2826.2010.01993.x
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发表时间：
2010-06-01
影响因子：
3.2
通讯作者：
Inoue, K.
中科院分区：
文献类型：
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作者：
Mochiduki, A.;Takeda, T.;Inoue, K.
催乳素释放肽（Prolactin-releasing peptide，PrRP）在催乳素分泌、应激反应、心血管调节和食物摄取抑制等方面具有重要作用。此外，PrRP敲除（KO）雄性小鼠从22周龄起就表现出肥胖并增加食物摄入量。胰岛素、瘦素、胆固醇和甘油三酯的血浆浓度在肥胖PrRP-KO小鼠中也增加。在肥胖PrRP KO小鼠中观察到脂肪肝、肥大的白色脂肪组织、棕色脂肪组织中解偶联蛋白1 mRNA表达降低和葡萄糖耐受不良。正如我们以前报道的，PrRP刺激促肾上腺皮质激素释放因子和调节下丘脑-垂体-肾上腺轴。因此，推测PrRP作为应激反应调节食物摄入和代谢。在本研究中，我们比较了PrRP-KO小鼠的血糖和血浆糖皮质激素浓度，发现PrRP-KO小鼠在束缚应激后显示出比野生型小鼠更高的血糖和皮质酮浓度。与此相反，两组下丘脑室旁核c-Fos表达和血浆促肾上腺皮质激素浓度无差异。这些结果表明，不同的应激反应，糖皮质激素分泌可能是由不同的反应，野生型和PrRP-KO小鼠之间的肾上腺诱导。因此，我们得出结论，PrRP-KO小鼠成为肥胖的结果增加的食物摄入量，代谢的变化，以及异常的应激反应，葡萄糖浓度和糖皮质激素分泌。
Prolactin-releasing peptide (PrRP) is known to have functions in prolactin secretion, stress responses, cardiovascular regulation and food intake suppression. In addition, PrRP-knockout (KO) male mice show obesity from the age of 22 weeks and increase their food intake. The plasma concentrations of insulin, leptin, cholesterol and triglyceride are also increased in obese PrRP-KO mice. Fatty liver, hypertrophied white adipose tissue, decreased uncoupling protein 1 mRNA expression in brown adipose tissue and glucose intolerance were observed in obese PrRP-KO mice. As we reported previously, PrRP stimulates corticotrophin-releasing factor and regulates the hypothalamic-pituitary-adrenal axis. Therefore, it is speculated that PrRP regulates both food intake and metabolism as a stress responses. In the present study, we compared blood glucose and plasma glucocorticoid concentrations in PrRP-KO mice, and found that PrRP-KO mice showed higher concentrations of blood glucose and corticosterone compared to wild-type mice after restraint stress. By contrast, there were no difference in c-Fos expression in the paraventricular hypothalamic nucleus and plasma adrenocorticotrophic hormone concentrations between the two groups. These results suggest that the different stress responses as to glucocorticoid secretion may be induced by different responses of the adrenal glands between wild-type and PrRP-KO mice. Thus, we conclude that PrRP-KO mice become obese as a result of increased food intake, a change in metabolism, and abnormal stress responses as to glucose concentration and glucocorticoid secretion.