Parathyroid hormone-related protein has an anorexigenic activity via activation of hypothalamic urocortins 2 and 3
Parathyroid hormone-related protein has an anorexigenic activity via activation of hypothalamic urocortins 2 and 3
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DOI：
10.1016/j.psyneuen.2010.02.003
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发表时间：
2010-09-01
影响因子：
3.7
通讯作者：
Inui, Akio
中科院分区：
文献类型：
--
作者：
Asakawa, Akihiro;Fujimiya, Mineko;Inui, Akio
据报道，癌症恶病质是癌症相关死亡的主要原因。由于发病机制尚未完全了解，只有少数有效的治疗方法已经建立。由于许多肿瘤产生甲状旁腺相关蛋白（PTHrP），因此在癌症恶病质中PTHrP的血浆浓度增加。我们测定了PTHrP腹腔注射后小鼠的摄食量、胃排空、条件性味觉厌恶（CTA）和下丘脑神经肽基因表达。我们给大鼠静脉注射PTHrP，检查胃十二指肠运动和迷走神经活动。我们还研究了PTHrP的长期给药是否会影响食物摄入量和体重。外周给予PTHrP通过减少食物摄入和胃排空诱导负能量平衡;然而，它不诱导CTA。其机制涉及通过迷走神经传入途径激活下丘脑尿皮质素2和3，并抑制胃十二指肠运动活动。PTHrP的持续输注减少了食物摄入和体重增加，同时减少了脂肪和骨骼肌。我们的研究结果表明，PTHrP影响的食物摄入量和体重，因此，PTHrP可以被认为是一个治疗癌症恶病质的目标。(C)2010爱思唯尔有限公司版权所有。
Cancer cachexia is reported to be a major cause of cancer-related death. Since the pathogenesis is not entirely understood, only few effective therapies have been established. Since myriad tumors produce parathyroid hormone-related protein (PTHrP), plasma concentrations of PTHrP are increased in cancer cachexia. We measured the food intake, gastric emptying, conditioned taste aversion (CTA), and gene expression of hypothalamic neuropeptides in mice after administering PTHrP intraperitoneally. We administered PTHrP intravenously in rats and examined the gastroduodenal motility and vagal nerve activities. We also examined whether chronic administration of PTHrP influenced the food intake and body weight. Peripherally administered PTHrP induced negative energy balance by decreasing the food intake and gastric emptying; however, it did not induce CTA. The mechanism involved the activation of hypothalamic urocortins 2 and 3 through vagal afferent pathways and the suppression of gastroduodenal motor activity. The continuous infusion of PTHrP reduced the food intake and body weight gain with a concomitant decrease in the fat and skeletal muscle. Our findings suggest that PTHrP influences the food intake and body weight; therefore, PTHrP can be considered as a therapeutic target for cancer cachexia. (C) 2010 Elsevier Ltd. All rights reserved.