Kisspeptin signaling in the amygdala modulates reproductive hormone secretion.
Kisspeptin signaling in the amygdala modulates reproductive hormone secretion.
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DOI：
10.1007/s00429-015-1024-9
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发表时间：
2016-05
影响因子：
3.1
通讯作者：
Dhillo WS
中科院分区：
文献类型：
--
作者：
Comninos AN;Anastasovska J;Sahuri-Arisoylu M;Li X;Li S;Hu M;Jayasena CN;Ghatei MA;Bloom SR;Matthews PM;O'Byrne KT;Bell JD;Dhillo WS
Kisspeptin（由KISS 1编码）是生殖功能的关键激活剂。kisspeptin的作用已经在下丘脑中得到了广泛的研究，但对其在大脑其他区域的意义知之甚少。KISS 1及其同源受体在杏仁核中表达，杏仁核是一种关键的边缘脑结构，具有对参与促性腺激素分泌的下丘脑中心的抑制性投射。因此，我们假设kisspeptin对下丘脑以外的神经元激活和生殖途径有影响，特别是在杏仁核内。为了测试这一点，我们映射脑神经元活动（使用锰增强MRI）与啮齿动物外周kisspeptin管理。我们还研究了功能相关性，通过测量促性腺激素的反应，直接内侧杏仁核（MeA）管理kisspeptin和kisspeptin拮抗剂。外周kisspeptin给药导致杏仁核中的信号强度与单独的载体相比显著降低。这与促黄体生成激素（LH）分泌增加有关。此外，MeA内给予kisspeptin导致LH分泌增加，而通过给予MeA内kisspeptin拮抗剂阻断杏仁核内的内源性kisspeptin信号传导降低LH分泌和LH脉冲频率。我们提供的证据首次表明，杏仁核内的神经元活动减少外周kisspeptin管理和kisspeptin信号传导杏仁核内的促性腺激素释放和脉动的调制。我们的数据表明，kisspeptin是生殖生理学的“主调节器”，整合边缘系统回路与促性腺激素释放激素神经元和生殖激素分泌的调节。
Kisspeptin (encoded by KISS1) is a crucial activator of reproductive function. The role of kisspeptin has been studied extensively within the hypothalamus but little is known about its significance in other areas of the brain. KISS1 and its cognate receptor are expressed in the amygdala, a key limbic brain structure with inhibitory projections to hypothalamic centers involved in gonadotropin secretion. We therefore hypothesized that kisspeptin has effects on neuronal activation and reproductive pathways beyond the hypothalamus and particularly within the amygdala. To test this, we mapped brain neuronal activity (using manganese-enhanced MRI) associated with peripheral kisspeptin administration in rodents. We also investigated functional relevance by measuring the gonadotropin response to direct intra-medial amygdala (MeA) administration of kisspeptin and kisspeptin antagonist. Peripheral kisspeptin administration resulted in a marked decrease in signal intensity in the amygdala compared to vehicle alone. This was associated with an increase in luteinizing hormone (LH) secretion. In addition, intra-MeA administration of kisspeptin resulted in increased LH secretion, while blocking endogenous kisspeptin signaling within the amygdala by administering intra-MeA kisspeptin antagonist decreased both LH secretion and LH pulse frequency. We provide evidence for the first time that neuronal activity within the amygdala is decreased by peripheral kisspeptin administration and that kisspeptin signaling within the amygdala contributes to the modulation of gonadotropin release and pulsatility. Our data suggest that kisspeptin is a ‘master regulator’ of reproductive physiology, integrating limbic circuits with the regulation of gonadotropin-releasing hormone neurons and reproductive hormone secretion.