INTRINSIC PULSATILE SECRETORY ACTIVITY OF IMMORTALIZED LUTEINIZING-HORMONE-RELEASING HORMONE-SECRETING NEURONS
INTRINSIC PULSATILE SECRETORY ACTIVITY OF IMMORTALIZED LUTEINIZING-HORMONE-RELEASING HORMONE-SECRETING NEURONS
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DOI：
10.1073/pnas.89.9.4149
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发表时间：
1992-05-01
影响因子：
11.1
通讯作者：
NEGROVILAR, A
中科院分区：
文献类型：
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作者：
WETSEL, WC;VALENCA, MM;NEGROVILAR, A
哺乳动物的生殖依赖于向垂体前叶间歇性输送促黄体激素释放激素（LHRH）。这种分泌方式是最大限度地使促性腺激素细胞对LHRH刺激敏感和调节促性腺激素基因表达所必需的。虽然LHRH分泌在本质上是脉动的，但脉冲发生器的起源尚不清楚。在这份报告中，我们表明，这个振荡器可以位于LHRH神经元网络。当将永生化的LHRH神经元置于灌流系统中时，LHRH在基础条件下以脉动方式分泌到培养基中。当从培养基中除去钙时，LHRH分泌和LHRH脉冲的数量减少。灌注也影响促LHRH的加工，因为当细胞从静态系统转移时，其加工产物的摩尔比变化很大。几种不同的细胞机制可能是这些分泌和加工变化的基础。荧光黄实验表明，一些细胞是染料耦合的。因此，这些细胞可以通过间隙连接电偶联，从而可以协调来自单个细胞的分泌。分泌也可以通过观察到的突触样接触同步。这些接触可以执行负反馈作用，不仅调节释放的LHRH的量，而且调节分泌的分子形式。LHRH神经元组织成相互连接的簇可以用于协调LHRH从单个细胞的分泌，从而在体内协调不同的功能，如青春期的开始，排卵的时间和哺乳期不孕的持续时间。
Mammalian reproduction is dependent upon intermittent delivery of luteinizing hormone-releasing hormone (LHRH) to the anterior-pituitary. This mode of secretion is required to sensitize maximally the gonadotrophs to LHRH stimulation and to regulate gonadotropin gene expression. While LHRH secretion is pulsatile in nature, the origin of the pulse generator is unknown. In this report, we show that this oscillator could be located within the LHRH neuronal network. When immortalized LHRH neurons are placed into a perifusion system, LHRH is secreted into the medium in a pulsatile fashion under basal conditions. LHRH secretion and the number of LHRH pulses are reduced when calcium is removed from the medium. Perifusion also influences pro-LHRH processing, since the molar ratio of its processed products varies dramatically when the cells are transferred from a static system. Several different cellular mechanisms may underlie these changes in secretion and processing. Lucifer yellow experiments reveal that some cells are dye-coupled. Hence, these cells could be electrically coupled through gap junctions such that secretion from individual cells could be coordinated. Secretion could also be synchronized through the observed synapse-like contacts. These contacts could perform a negative-feedback role to regulate not only the amount of LHRH released but also the molecular forms secreted. The organization of LHRH neurons into interconnected clusters could serve to coordinate LHRH secretion from individual cells and, thereby, orchestrate functions in vivo as diverse as the onset of puberty, the timing of ovulation, and the duration of lactational infertility.