Effects of kisspeptin-10 on the electrophysiological manifestation of gonadotropin-releasing hormone pulse generator activity in the female rat

Effects of kisspeptin-10 on the electrophysiological manifestation of gonadotropin-releasing hormone pulse generator activity in the female rat
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DOI:
10.1210/en.2007-1505
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发表时间:
2008-03-01
期刊:
影响因子:
4.8
通讯作者:
O'Byrne, Kevin T.
O'Byrne, Kevin T.
中科院分区:
医学2区
文献类型:
--
作者:
Kinsey-Jones, James S.;Li, Xiao Feng;O'Byrne, Kevin T.

文献摘要

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kisspeptin通过对下丘脑GnRH神经系统的作用,在刺激促性腺激素分泌方面非常有效。由于GnRH脉冲发生器的生理频率是控制生殖过程的控制系统的关键组成部分,本研究的目的是研究kisspeptin-10对脉动性LH分泌和GnRH脉冲发生器活性的电生理表现的影响,以确定频率调节作用。成年Sprague Dawley大鼠切除卵巢,在弓形核中长期植入电极,记录下丘脑多单位电活动的特征性增加,同时开始在外周血中测量每个LH脉冲和/或留置心导管,每5分钟采集血液样本(25 μ 1),持续6-7小时,用于测量LH。静脉输注kisspeptin-10(7.5、35和100 nmol)诱导黄体生成素分泌剂量依赖性增加。kisspeptin-10 (100 nmol)对LH分泌的刺激作用被GnRH拮抗剂cetrorelix阻断,排除了对促性腺激素的单一作用。然而,令人意外的是,kisspeptin-10 (100 nmol)给药后LH释放的显著增加并没有伴随着多单位电活动频率的任何变化。因此,kisspeptin-10似乎不太可能对雌性大鼠GnRH脉冲发生器的活性有明显的频率调节作用。
Kisspeptins are extraordinarily potent in stimulating gonadotropic hormone secretion via an action on the hypothalamic GnRH neural system. Because the physiological frequency of the GnRH pulse generator is a critical component of the control system that governs reproductive processes, the aim of this study was to examine the effect of kisspeptin-10 on pulsatile LH secretion and on the electrophysiological manifestation of GnRH pulse generator activity to determine frequency modulatory effects. Adult Sprague Dawley rats were ovariectomized and chronically implanted with electrodes in the arcuate nucleus to record the characteristic increases in hypothalamic multiunit electrical activity volleys coincident with the initiation of each LH pulse measured in peripheral blood and/or indwelling cardiac catheters for the collection of blood samples (25 mu 1) every 5 min for 6-7 h for the measurement of LH. Intravenous infusion of kisspeptin-10 (7.5,35, and 100 nmol) induced a dose-dependent increase in LH secretion. The stimulatory effect of kisspeptin-10 (100 nmol) on LH secretion was blocked by the GnRH antagonist cetrorelix, precluding a singular action on gonadotropes. Unexpectedly, however, the marked increase in LH release in response to kisspeptin-10 (100 nmol) administration was not accompanied by any change in multiunit electrical activity volley frequency. It seem unlikely, therefore, that kisspeptin-10 has an appreciable frequency modulatory effect on GnRH pulse generator activity in the female rat.