Estradiol-17 beta and mu-opioid peptides rapidly hyperpolarize GnRH neurons: a cellular mechanism of negative feedback?
Estradiol-17 beta and mu-opioid peptides rapidly hyperpolarize GnRH neurons: a cellular mechanism of negative feedback?
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DOI：
10.1210/endo.136.5.7720682
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发表时间：
1995-05
期刊：
影响因子：
4.8
通讯作者：
A. Lagrange;O. Rønnekleiv;M. Kelly
中科院分区：
文献类型：
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作者：
A. Lagrange;O. Rønnekleiv;M. Kelly
HPG轴的控制涉及E2对LH（GnRH）释放的快速（30分钟）抑制。这种效应的时间过程比E2作用的纯转录机制预期的要快。为了阐明E2的作用机制，在豚鼠下丘脑GnRH神经元上进行了TTX的细胞内记录。μ-阿片激动剂DAMGO（Tyr-D-Ala-Gly-MePhe-Gly-ol，9 mV）和GABAB激动剂巴氯芬（18 mV）通过打开K+通道直接使这些神经元超极化。用纳洛酮（Ke = 2.4 nM）进行的Schild分析证实μ-阿片受体介导DAMGO的作用。E2还通过开放K+通道直接使GnRH神经元超极化。结合先前显示E2改变μ阿片效力的快速作用的工作（1），提出了一种模型，其中E2通过平行的、可能协同的途径快速抑制GnRH神经元。
Control of the HPG axis involves a rapid (30 min) inhibition of LH (GnRH) release by E2. The time course of this effect is faster than expected for a purely transcriptional mechanism of E2 action. To elucidate the mechanism of E2 action, intracellular recordings in TTX were performed in guinea pig hypothalamic GnRH neurons. These neurons were directly hyperpolarized by both the mu-opioid agonist, DAMGO (Tyr-D-Ala-Gly-MePhe-Gly-ol, 9 mV) and the GABAB agonist, baclofen (18 mV) by opening K+ channels. Schild analysis with naloxone (Ke = 2.4 nM) confirmed that mu-opioid receptors mediated the effect of DAMGO. E2 also directly hyperpolarized GnRH neurons by opening K+ channels. Coupled with previous work showing a rapid effect of E2 to alter mu-opioid potency (1), a model is presented in which E2 rapidly inhibits GnRH neurons through parallel, possibly synergistic pathways.