Activation of Neurokinin 3 Receptors in the Median Preoptic Nucleus Decreases Core Temperature in the Rat
Activation of Neurokinin 3 Receptors in the Median Preoptic Nucleus Decreases Core Temperature in the Rat
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DOI：
10.1210/en.2011-1492
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发表时间：
2011-12-01
期刊：
影响因子：
4.8
通讯作者：
Rance, Naomi E.
中科院分区：
文献类型：
--
作者：
Dacks, Penny A.;Krajewski, Sally J.;Rance, Naomi E.
雌激素对体温调节有明显的作用，如绝经期妇女雌激素戒断后继发潮热的发生所示。由于神经激肽B（NKB）基因的表达显着增加漏斗（弓状）核绝经后妇女，并调制雌激素撤退和更换在多个物种，我们假设，NKB神经元可以发挥作用，在产生潮红。然而，没有关于主要NKB受体[神经激肽3受体（NK（3）R）]是否在任何物种中调节体温的信息。在这里，我们确定了选择性NK（3）R激动剂（senktide）微量输注到大鼠正中视前核（MnPO），在热防御途径的一个重要网站的影响。向大鼠体内微量输注Senktide MnPO以剂量依赖性方式降低核心温度。senktide诱导的低体温在有和没有17 β-雌二醇替代的卵巢切除大鼠中是相似的。在环境温度为29.0 ℃的大鼠中，与21.5 ℃相比，森克肽的降温作用延长。Senktide微量输注也改变了暴露于29.0 ℃但不暴露于21.5 ℃环境温度的大鼠的尾部皮肤血管舒缩。在不同的环境温度下的senktide的影响的比较表明，低温不是次要的体温调节失败或减少冷诱导产热。除了非常轻微的饮酒增加外，senktide微量输注不会影响行为。末端荧光葡聚糖微输注显示针对MnPO和相邻的隔膜，免疫组织化学研究表明，senktide诱导MnPO中Fos激活的显着增加。由于MnPO神经元表达NK（3）R免疫反应性，因此森克肽对MnPO Fos的诱导可能是直接作用。通过证明MnPO中的NK（3）R活化调节体温，这些研究支持下丘脑NKB神经元可能参与更年期潮红产生的假设。（内分泌学152：4894-4905，2011）
Estrogens have pronounced effects on thermoregulation, as illustrated by the occurrence of hot flushes secondary to estrogen withdrawal in menopausal women. Because neurokinin B (NKB) gene expression is markedly increased in the infundibular (arcuate) nucleus of postmenopausal women, and is modulated by estrogen withdrawal and replacement in multiple species, we have hypothesized that NKB neurons could play a role in the generation of flushes. There is no information, however, on whether the primary NKB receptor [neurokinin 3 receptor (NK(3)R)] modulates body temperature in any species. Here, we determine the effects of microinfusion of a selective NK(3)R agonist (senktide) into the rat median preoptic nucleus (MnPO), an important site in the heat-defense pathway. Senktide microinfusion into the rat MnPO decreased core temperature in a dose-dependent manner. The hypothermia induced by senktide was similar in ovariectomized rats with and without 17 beta-estradiol replacement. The hypothermic effect of senktide was prolonged in rats exposed to an ambient temperature of 29.0 C, compared with 21.5 C. Senktide microinfusion also altered tail skin vasomotion in rats exposed to an ambient temperature of 29.0 but not 21.5 C. Comparisons of the effects of senktide at different ambient temperatures indicated that the hypothermia was not secondary to thermoregulatory failure or a reduction in cold-induced thermogenesis. Other than a very mild increase in drinking, senktide microinfusion did not affect behavior. Terminal fluorescent dextran microinfusion showed targeting of the MnPO and adjacent septum, and immunohistochemical studies revealed that senktide induced a marked increase in Fos-activation in the MnPO. Because MnPO neurons expressed NK(3)R-immunoreactivity, the induction of MnPO Fos by senktide is likely a direct effect. By demonstrating that NK(3)R activation in the MnPO modulates body temperature, these studies support the hypothesis that hypothalamic NKB neurons could be involved in the generation of menopausal flushes. (Endocrinology 152: 4894-4905, 2011)