University of Cambridge Metabolic Research Laboratories, Institute of Metabolic Science, Addenbrooke's Treatment Centre, Addenbrooke's Hospital, Cambridge, UK.
J Neuroendocrinol. 2010 Mar;22(3):181-7. doi: 10.1111/j.1365-2826.2009.01951.x. Epub 2009 Dec 23.
Growing evidence suggests the tachykinin neurokinin B (NKB) may modulate gonadotrophin secretion and play a role in sex-steroid feedback within the reproductive axis. NKB signalling has recently been identified as being necessary for normal human reproductive function, although the precise mechanisms underpinning this role remain to be established. We have used rodents to explore further the role of NKB within the reproductive axis. In particular, we have studied its interactions with kisspeptin, a neuropeptide essential for reproductive function in rodent and human with close anatomical links to NKB within the hypothalamus. Intraperitoneal administration of NKB (50 nmol) to male mice had no effect on circulating luteinsing hormone (LH) levels and, although i.p. kisspeptin (15 nmol) increased LH five-fold, co-administration of NKB and kisspeptin was indistinguishable from kisspeptin alone. Intracerebroventricular administration of NKB (10 nmol) to male mice also had no effect on LH levels, with 1 nmol kisspeptin i.c.v. significantly increasing LH compared to control (0.37 +/- 0.18 versus 5.11 +/- 0.28 ng/ml, respectively). Interestingly, i.c.v. co-administration of NKB and kisspeptin caused a significant increase in LH concentrations compared to kisspeptin alone (8.96 +/- 1.82 versus 5.11 +/- 0.28 ng/ml respectively). We used hypothalamic explants from rats to assess the effect of NKB on gonadotrpohin-releasing hormone (GnRH) secretion ex vivo. Doses of NKB up to 1000 nm failed to stimulate GnRH secretion, whereas 100 nm kisspeptin robustly increased GnRH secretion. Of note, co-administration of NKB with kisspeptin abrogated the effect of kisspeptin, producing no GnRH release above basal state. Finally, we analysed the expression of Tac2/Tacr3 (genes encoding NKB and NK3R, respectively) within the arcuate nucleus in different nutritional states. After a 48-h fast, the expression of both Tac2 and Tacr3 showed a significant increase, in contrast to levels of Kiss1 and Kiss1r mRNA, which remained unchanged. In male rodent models, NKB and kisspeptin have different effects upon gonadotrophin release and appear to interact in a complex manner.
越来越多的证据表明，速激肽神经激肽 B（NKB）可能调节促性腺激素的分泌，并在生殖轴内的性激素反馈中发挥作用。NKB 信号最近被确定为正常人类生殖功能所必需的，但支持这一作用的精确机制仍有待确定。我们使用啮齿动物进一步研究 NKB 在生殖轴中的作用。特别是，我们研究了它与 kisspeptin 的相互作用，kisspeptin 是一种在啮齿动物和人类生殖功能中必不可少的神经肽，在下丘脑内与 NKB 具有密切的解剖联系。腹腔内给予雄性小鼠 NKB（50 nmol）对循环黄体生成素（LH）水平没有影响，尽管腹腔内给予 kisspeptin（15 nmol）使 LH 增加五倍，但 NKB 和 kisspeptin 的共同给予与 kisspeptin 单独给予没有区别。向雄性小鼠脑室内给予 NKB（10 nmol）也对 LH 水平没有影响，1 nmol kisspeptin 脑室内显著增加 LH 与对照相比（分别为 0.37 +/- 0.18 与 5.11 +/- 0.28 ng/ml）。有趣的是，与 kisspeptin 单独给予相比，脑室内共同给予 NKB 和 kisspeptin 导致 LH 浓度显著增加（分别为 8.96 +/- 1.82 与 5.11 +/- 0.28 ng/ml）。我们使用大鼠下丘脑切片评估 NKB 对 GnRH 分泌的影响。高达 1000nm 的 NKB 剂量未能刺激 GnRH 分泌，而 100nm kisspeptin 则强烈增加 GnRH 分泌。值得注意的是，NKB 与 kisspeptin 共同给予消除了 kisspeptin 的作用，没有产生高于基础状态的 GnRH 释放。最后，我们分析了不同营养状态下弓状核中 Tac2/Tacr3（分别编码 NKB 和 NK3R 的基因）的表达。禁食 48 小时后，Tac2 和 Tacr3 的表达均显著增加，而 Kiss1 和 Kiss1r mRNA 的水平保持不变。在雄性啮齿动物模型中，NKB 和 kisspeptin 对促性腺激素释放有不同的影响，并且似乎以复杂的方式相互作用。
