Han Seong-Kyu, Herbison Allan E
Department of Oral Physiology and Institute of Oral Bioscience, School of Dentistry, Chonbuk National University, Jeonju 561-756, South Korea.
Endocrinology. 2008 Mar;149(3):1129-35. doi: 10.1210/en.2007-1241. Epub 2007 Dec 13.
Norepinephrine (NE) is considered to exert an important modulatory influence upon the activity of GnRH neurons. In the present study, we used a transgenic GnRH-green fluorescent protein mouse model to examine the effects of NE on the electrical excitability of GnRH neurons in male and female mice. Gramicidin-perforated patch recordings demonstrated that NE (10-100 mum) exerted a robust membrane hyperpolarization, with associated suppression of firing, in more than 85% of male prepubertal and adult GnRH neurons (n = 25). The same hyperpolarizing action was observed in female GnRH neurons from diestrous (91%, n = 11), proestrous (50%, n = 14), estrous (77%, n = 13), and ovariectomized (82%, n = 11) mice. A subpopulation (<10%) of silent GnRH neurons in all groups responded to NE with hyperpolarization followed by the initiation of firing upon NE washout. The hyperpolarizing actions of NE were mimicked by alpha1-adrenergic (phenylephrine) and beta-adrenergic (isoproterenol) receptor agonists, but alpha2 receptor activation (guanabenz) had no effect. Approximately 75% of the NE-evoked hyperpolarization was blocked by the alpha1 receptor antagonist prazosin, and 75% of GnRH neurons responded to both phenylephrine and isoproterenol. These findings indicate that NE acts through both alpha1- and beta-adrenergic receptors located on the soma/dendrites of GnRH neurons to directly suppress their excitability throughout the estrous cycle and after ovariectomy. These data force a reanalysis of existing models explaining the effects of NE on gonadotropin secretion.
去甲肾上腺素（NE）被认为对促性腺激素释放激素（GnRH）神经元的活动发挥重要的调节作用。在本研究中，我们使用转基因GnRH-绿色荧光蛋白小鼠模型来研究NE对雄性和雌性小鼠GnRH神经元电兴奋性的影响。短杆菌肽穿孔膜片钳记录表明，NE（10 - 100 μM）在超过85%的雄性青春期前和成年GnRH神经元（n = 25）中引起强烈的膜超极化，并伴有放电抑制。在处于动情后期（91%，n = 11）、动情前期（50%，n = 14）、动情期（77%，n = 13）和卵巢切除术后（82%，n = 11）的雌性GnRH神经元中也观察到了同样的超极化作用。所有组中一小部分（<10%）沉默的GnRH神经元对NE产生超极化反应，随后在NE洗脱后开始放电。NE的超极化作用可被α1肾上腺素能（去氧肾上腺素）和β肾上腺素能（异丙肾上腺素）受体激动剂模拟，但α2受体激活（胍那苄）没有效果。约75%的NE诱发的超极化被α1受体拮抗剂哌唑嗪阻断，75%的GnRH神经元对去氧肾上腺素和异丙肾上腺素均有反应。这些发现表明，NE通过位于GnRH神经元胞体/树突上的α1和β肾上腺素能受体发挥作用，在整个发情周期和卵巢切除术后直接抑制其兴奋性。这些数据促使对解释NE对促性腺激素分泌影响的现有模型进行重新分析。
