Neurokinin B and Dynorphin A in Kisspeptin Neurons of the Arcuate Nucleus Participate in Generation of Periodic Oscillation of Neural Activity Driving Pulsatile Gonadotropin-Releasing Hormone Secretion in the Goat
Neurokinin B and Dynorphin A in Kisspeptin Neurons of the Arcuate Nucleus Participate in Generation of Periodic Oscillation of Neural Activity Driving Pulsatile Gonadotropin-Releasing Hormone Secretion in the Goat
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DOI：
10.1523/jneurosci.5848-09.2010
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发表时间：
2010-02-24
影响因子：
5.3
通讯作者：
Okamura, Hiroaki
中科院分区：
文献类型：
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作者：
Wakabayashi, Yoshihiro;Nakada, Tomoaki;Okamura, Hiroaki
基底前脑中的促性腺激素释放激素（GnRH）神经元是大脑调节生殖的最终共同途径。GnRH的分泌是以脉动的方式发生的，间接证据表明弓状核（ARC）中的kisspeptin神经元是驱动GnRH脉动分泌的中枢起搏器。本研究的目的是研究kisspeptin、神经激肽B（NKB）和强啡肽A（Dyn）在山羊ARC神经元中的可能共表达，并评价它们在GnRH脉冲产生中的潜在作用。使用双重和三重标记，我们证实，所有三种神经肽共表达在同一个群体的神经元。使用电生理技术记录下丘脑内侧基底部的多单位活动（MUA），我们发现，在卵巢切除动物中，MUA的爆发以规则的时间间隔发生，并且这些重复的爆发（齐射）总是与黄体生成素（LH）的离散脉冲（通过推论GnRH）相关。此外，频率的MUA截击减少性腺类固醇，这表明截击反映了激素敏感的神经元，调节GnRH分泌的节律性放电。最后，我们观察到，中枢给予Dyn-I抑制MUA的齐射和脉冲式LH分泌，而NKB诱导MUA齐射。这些观察结果与ARC中的kisspeptin神经元驱动GnRH和LH脉动分泌的假设一致，并表明在这些神经元中表达的NKB和Dyn参与产生kisspeptin的节律性放电的过程。
Gonadotropin-releasing hormone (GnRH) neurons in the basal forebrain are the final common pathway through which the brain regulates reproduction. GnRH secretion occurs in a pulsatile manner, and indirect evidence suggests the kisspeptin neurons in the arcuate nucleus (ARC) serve as the central pacemaker that drives pulsatile GnRH secretion. The purpose of this study was to investigate the possible coexpression of kisspeptin, neurokinin B (NKB), and dynorphin A (Dyn) in neurons of the ARC of the goat and evaluate their potential roles in generating GnRH pulses. Using double and triple labeling, we confirmed that all three neuropeptides are coexpressed in the same population of neurons. Using electrophysiological techniques to record multiple-unit activity (MUA) in the medial basal hypothalamus, we found that bursts of MUA occurred at regular intervals in ovariectomized animals and that these repetitive bursts (volleys) were invariably associated with discrete pulses of luteinizing hormone (LH) (and by inference GnRH). Moreover, the frequency of MUA volleys was reduced by gonadal steroids, suggesting that the volleys reflect the rhythmic discharge of steroid-sensitive neurons that regulate GnRH secretion. Finally, we observed that central administration of Dyn-inhibit MUA volleys and pulsatile LH secretion, whereas NKB induced MUA volleys. These observations are consistent with the hypothesis that kisspeptin neurons in the ARC drive pulsatile GnRH and LH secretion, and suggest that NKB and Dyn expressed in those neurons are involved in the process of generating the rhythmic discharge of kisspeptin.