The Dorsomedial Suprachiasmatic Nucleus Times Circadian Expression of Kiss1 and the Luteinizing Hormone Surge
The Dorsomedial Suprachiasmatic Nucleus Times Circadian Expression of Kiss1 and the Luteinizing Hormone Surge
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DOI：
10.1210/en.2011-1857
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发表时间：
2012-06-01
期刊：
影响因子：
4.8
通讯作者：
de la Iglesia, Horacio O.
中科院分区：
文献类型：
--
作者：
Smarr, Benjamin L.;Morris, Emma;de la Iglesia, Horacio O.
哺乳动物的排卵是由视交叉上核（SCN）中的主生物钟控制的。GnRH神经元代表了大脑触发排卵的会聚途径，但SCN如何乘以GnRH神经元尚不清楚。我们测试的假设，表达kisspeptin的神经元，由Kiss 1基因编码的神经肽和必要的激活GnRH细胞在排卵期间，代表一个中继站的昼夜信息，排卵时间。我们首先表明，Kiss 1表达的昼夜节律增加，以及GnRH细胞的激活，依赖于完整的同侧SCN的神经输入。第二，通过desperizing的背内侧（DM）和腹外侧（VL）的SCN的子区域，我们表明，时钟驻留在dmSCN的行为独立的光暗周期，和vlSCN，时间Kiss 1表达在下丘脑腹侧脑室周围核，这种节奏总是在与LH浪涌的阶段。此外，我们表明，虽然LH浪涌的时间是由dmSCN，其幅度可能取决于vlSCN和dmSCN之间的相位相干性。我们的研究结果表明，尽管dmSCN神经元振荡器足以通过输入下丘脑前腹侧室周核中的kisspeptin细胞来计时LH峰，但dmSCN，vlSCN，和额外的-他们还认为，与夜班工作相关的女性生殖障碍可能源于主脑内次区域振荡器之间的去极化，生物钟（内分泌学153：2839-2850，2012）
Ovulation in mammals is gated by a master circadian clock in the suprachiasmatic nucleus (SCN). GnRH neurons represent the converging pathway through which the brain triggers ovulation, but precisely how the SCN times GnRH neurons is unknown. We tested the hypothesis that neurons expressing kisspeptin, a neuropeptide coded by the Kiss1 gene and necessary for the activation of GnRH cells during ovulation, represent a relay station for circadian information that times ovulation. We first show that the circadian increase of Kiss1 expression, as well as the activation of GnRH cells, relies on intact ipsilateral neural input from the SCN. Second, by desynchronizing the dorsomedial (dm) and ventrolateral (vl) subregions of the SCN, we show that a clock residing in the dmSCN acts independently of the light-dark cycle, and the vlSCN, to time Kiss1 expression in the anteroventral periventricular nucleus of the hypothalamus and that this rhythm is always in phase with the LH surge. In addition, we show that although the timing of the LH surge is governed by the dmSCN, its amplitude likely depends on the phase coherence between the vlSCN and dmSCN. Our results suggest that whereas dmSCN neuronal oscillators are sufficient to time the LH surge through input to kisspeptin cells in the anteroventral periventricular nucleus of the hypothalamus, the phase coherence among dmSCN, vlSCN, and extra-SCN oscillators is critical for shaping it. They also suggest that female reproductive disorders associated with nocturnal shift work could emerge from the desynchronization between subregional oscillators within the master circadian clock. (Endocrinology 153: 2839-2850, 2012)