Circadian Control of Kisspeptin and a Gated GnRH Response Mediate the Preovulatory Luteinizing Hormone Surge
Circadian Control of Kisspeptin and a Gated GnRH Response Mediate the Preovulatory Luteinizing Hormone Surge
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DOI：
10.1210/en.2010-0943
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发表时间：
2011-02-01
期刊：
影响因子：
4.8
通讯作者：
Kriegsfeld, Lance J.
中科院分区：
文献类型：
--
作者：
Williams, Wilbur P., III;Jarjisian, Stephan G.;Kriegsfeld, Lance J.
在自发排卵的啮齿动物中，排卵前LH峰在发情前期由源自视交叉上核（SCN）中的昼夜节律钟的定时刺激信号启动。本研究探讨了kisspeptin是否是连接SCN的GnRH系统刺激叙利亚仓鼠（Mesocricetus auratus）排卵的重要神经回路的一部分。Kisspeptin神经元表现出雌激素依赖性的细胞活动的日常模式与LH峰的昼夜节律控制中的作用一致。SCN通过加压素能（AVP）而不是血管活性肠多肽能投射靶向kisspeptin神经元。由于AVP给药只能在一天中的有限时间内刺激LH峰，我们研究了对AVP的反应在kisspeptin和/或GnRH神经元水平上门控的可能性。在早上（当AVP不能启动LH峰时）和下午（当AVP注射刺激LH峰时）施用AVP后，评估Kisspeptin和GnRH激活。Kisspeptin，但不是GnRH，细胞活性在早晨注射AVP后上调，表明对SCN信号的时间依赖性敏感性在GnRH神经元内门控，但不是Kisspeptin神经元。为了支持这种可能性，我们发现GnRH系统对kisspeptin刺激的敏感性每天都有明显的变化，下午的敏感性最高。总之，这些研究揭示了一种新的排卵控制机制与昼夜节律系统，kisspeptin信号传导和GnRH门控控制机制之间的相互作用。（内分泌学152：595-606，2011）
In spontaneously ovulating rodents, the preovulatory LH surge is initiated on the day of proestrus by a timed, stimulatory signal originating from the circadian clock in the suprachiasmatic nucleus (SCN). The present studies explored whether kisspeptin is part of the essential neural circuit linking the SCN to the GnRH system to stimulate ovulation in Syrian hamsters (Mesocricetus auratus). Kisspeptin neurons exhibit an estrogen-dependent, daily pattern of cellular activity consistent with a role in the circadian control of the LH surge. The SCN targets kisspeptin neurons via vasopressin-ergic (AVP), but not vasoactive intestinal polypeptide-ergic, projections. Because AVP administration can only stimulate the LH surge during a restricted time of day, we examined the possibility that the response to AVP is gated at the level of kisspeptin and/or GnRH neurons. Kisspeptin and GnRH activation were assessed after the administration of AVP during the morning (when AVP is incapable of initiating the LH surge) and the afternoon (when AVP injections stimulate the LH surge). Kisspeptin, but not GnRH, cellular activity was up-regulated after morning injections of AVP, suggesting that time-dependent sensitivity to SCN signaling is gated within GnRH but not kisspeptin neurons. In support of this possibility, we found that the GnRH system exhibits pronounced daily changes in sensitivity to kisspeptin stimulation, with maximal sensitivity in the afternoon. Together these studies reveal a novel mechanism of ovulatory control with interactions among the circadian system, kisspeptin signaling, and a GnRH gating mechanism of control. (Endocrinology 152: 595-606, 2011)