Development of Gonadotropin-Releasing Hormone-1 Secretion in Mouse Nasal Explants
Development of Gonadotropin-Releasing Hormone-1 Secretion in Mouse Nasal Explants
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DOI：
10.1210/en.2008-1711
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发表时间：
2009-07-01
期刊：
影响因子：
4.8
通讯作者：
Duittoz, Anne H.
中科院分区：
文献类型：
--
作者：
Constantin, Stephanie;Caraty, Alain;Duittoz, Anne H.
GnRH-1的脉冲式释放对于刺激垂体前叶的促性腺激素是至关重要的。这种分泌模式似乎是GnRH-1神经元固有的，然而，这种偶发性释放的机制仍然未知。在猴鼻外植体中，GnRH-1群体表现出与GnRH-1释放相同周期的同步钙事件，表明存在联系，尽管事件的顺序尚不清楚。小鼠鼻外植体中的GnRH-1神经元也表现出同步钙事件。在本工作中，GnRH-1释放在小鼠鼻外植体使用放射免疫学和其与钙信号的关系进行了分析。GnRH-1神经元在体外早在3天（div）就产生了偶发性释放，并在整个研究期间（3-21 div）保持这种释放。脉冲频率保持恒定，表明脉冲发生器在早期发育阶段起作用。与此相反，脉冲幅度增加2倍之间3和7 div，并再次之间7和14 div，这表明成熟的合成和/或分泌机制。为了评估这些可能性，测量了总GnRH-1含量。在7 - 14 div之间仅检测到GnRH-1含量的小幅增加，而在14 - 21 div之间出现大幅增加。这些数据表明，GnRH-1含量不是7格脉冲幅度的限制因素，但分泌机制在3至14格之间成熟。kisspeptin-10的应用揭示了GnRH-1神经元将来自天然配体的信号整合到分泌反应中的能力。最后，同时采样的介质和钙成像记录表明，同步的钙事件和分泌事件是一致的。（内分泌学150：3221-3227，2009）
Pulsatile release of GnRH-1 is critical to stimulate gonadotropes of the anterior pituitary. This secretory pattern seems to be inherent to GnRH-1 neurons, however, the mechanisms underlying such episodical release remain unknown. In monkey nasal explants, the GnRH-1 population exhibits synchronized calcium events with the same periodicity as GnRH-1 release, suggesting a link, though the sequence of events was unclear. GnRH-1 neurons in mouse nasal explants also exhibit synchronized calcium events. In the present work, GnRH-1 release was assayed in mouse nasal explants using radioimmunology and its relationship with calcium signaling analyzed. GnRH-1 neurons generated episodical release as early as 3 d in vitro (div) and maintained such release throughout the period studied (3-21 div). The pulse frequency remained constant, suggesting that the pulse generator is operative at an early developmental stage. In contrast, pulse amplitude increased 2-fold between 3 and 7 div, and again between 7 and 14 div, suggesting maturation in synthesizing and/or secretory mechanisms. To evaluate these possibilities, total GnRH-1 content was measured. Only a small increase in GnRH-1 content was detected between 7 and 14 div, whereas a large increase occurred between 14 and 21 div. These data indicate that GnRH-1 content was not a limiting factor for the amplitude of the pulses at 7 div but that the secretory mechanisms mature between 3 and 14 div. The application of kisspeptin-10 revealed the ability of GnRH-1 neurons to integrate signals from natural ligands into a secretory response. Finally, simultaneous sampling of medium and calcium imaging recordings indicated that the synchronized calcium events and secretory events are congruent. (Endocrinology 150: 3221-3227, 2009)