Cetrorelix, a Gonadotropin-Releasing Hormone Antagonist, Induces the Expression of Melatonin Receptor 1a in the Gonadotropin-Releasing Hormone Neuronal Cell Line GT1-7
Cetrorelix, a Gonadotropin-Releasing Hormone Antagonist, Induces the Expression of Melatonin Receptor 1a in the Gonadotropin-Releasing Hormone Neuronal Cell Line GT1-7
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DOI：
10.1159/000231993
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发表时间：
2009-01-01
影响因子：
4.1
通讯作者：
Kato, Masakatsu
中科院分区：
文献类型：
--
作者：
Ishii, Hirotaka;Sato, Shun;Kato, Masakatsu
褪黑激素与生殖系统的控制有关，褪黑激素对促性腺激素释放激素（GnRH）神经元的调节作用被认为是通过传入神经元间接介导的。然而，我们以前的研究表明，在成年大鼠GnRH神经元中，褪黑激素对A型γ-氨基丁酸（GABA）受体（GABA（A）R）电流的性二态性调制，以及褪黑激素1a受体（MT 1）在雄性GnRH神经元中的优先表达。本研究利用永生化GnRH神经元（GT1 - 7细胞）研究了GnRH神经元褪黑素受体表达的调控机制。与内源性GnRH神经元一样，GT1 - 7细胞表达GnRH和GnRH受体mRNA，表明细胞具有自我刺激系统。2-iodomelatonin结合试验和RT-PCR分析表明，细胞既不表达MT1也不表达MT2。然而，治疗的GT1 - 7细胞与GnRH拮抗剂西曲瑞克显着增加2-碘褪黑激素的结合，并诱导时间和浓度依赖性MT1 mRNA的表达。然后使用穿孔膜片钳技术测量GABA（A）R电流，以检查西曲瑞克治疗是否改变对褪黑激素的反应。褪黑激素增强1 μ M西曲瑞克处理24 h的GT1 - 7细胞的GABA（A）R电流，而褪黑激素降低未用西曲瑞克处理的细胞的电流，可能通过受体非依赖性过程。提示GnRH通过自分泌-旁分泌机制下调MT 1的表达，并改变褪黑素对GABA（A）R电流的调节作用。这些结果可能为成年大鼠GnRH神经元对褪黑激素的性二型反应提供了一种可能的机制。版权所有（C）2009 S. Karger AG，巴塞尔
Melatonin has been implicated in the control of the reproductive system, and the modulatory actions of melatonin on gonadotropin-releasing hormone (GnRH) neurons have been assumed to be indirectly mediated through afferent neurons. However, our previous studies demonstrate sexually dimorphic modulation of A-type gamma-aminobutyric acid (GABA) receptor (GABA(A)R) currents by melatonin in adult rat GnRH neurons and a preferential expression of melatonin 1a receptor (MT1) in male GnRH neurons. Using immortalized GnRH neurons (GT1-7 cells), the present study investigated the mechanism by which the expression of melatonin receptors is regulated in GnRH neurons. Like endogenous GnRH neurons, GT1-7 cells express both GnRH and GnRH receptor mRNAs, indicating that the cells have a self-stimulatory system. A 2-iodomelatonin binding assay and RT-PCR analysis demonstrated that the cells expressed neither MT1 nor MT2. However, treatment of GT1-7 cells with the GnRH antagonist cetrorelix significantly increased 2-iodomelatonin binding and induced a time- and concentration-dependent MT1 mRNA expression. The GABA(A)R currents were then measured using a perforated patch-clamp technique to examine whether the treatment with cetrorelix changed the responses to melatonin. Melatonin augmented the GABA(A)R currents in GT1-7 cells treated with 1 mu M cetrorelix for 24 h, while melatonin decreased the currents in the cells not treated with cetrorelix, probably via receptor-independent processes. The present results suggest that GnRH downregulates the expression of MT1 via an autocrine-paracrine mechanism in GT1-7 cells, and modifies the melatonin-induced modulation of GABA(A)R currents. These findings may provide one possible mechanism for the sexually dimorphic responses to melatonin in adult rat GnRH neurons. Copyright (C) 2009 S. Karger AG, Basel