Gonadotropin-releasing hormone (GnRH) receptor expression and membrane signaling in early embryonic GnRH neurons: Role in pulsatile neurosecretion
Gonadotropin-releasing hormone (GnRH) receptor expression and membrane signaling in early embryonic GnRH neurons: Role in pulsatile neurosecretion
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DOI：
10.1210/me.2003-0321
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发表时间：
2004-07-01
影响因子：
--
通讯作者：
Catt, KJ
中科院分区：
文献类型：
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作者：
Martinez-Fuentes, AJ;Hu, L;Catt, KJ
下丘脑神经元脉冲式分泌GnRH的特征依赖于GnRH与其受体之间的自分泌相互作用。在胚胎大鼠嗅板GnRH神经元的特性研究中，探讨了这种自我调节过程的个体发生和功能。免疫细胞化学鉴定的分析，激光捕获胎鼠下丘脑GnRH神经元，和嗅板衍生的GnRH神经元鉴别的差分干涉对比显微镜，表现出共表达的mRNA编码的GnRH和I型受体。基板衍生和永生化的GnRH神经元（GT1 - 7细胞）都表现出自发的电活动，GnRH激动剂治疗刺激。这种诱发的反应，以及基础神经元放电，被取消的治疗与GnRH拮抗剂。GnRH刺激引起双相细胞内钙（[Ca 2 +]（i））反应，拮抗剂处理降低了基础和GnRH刺激的[Ca 2 +]（i）水平。Perifused文化释放GnRH在脉动的方式是高度依赖于细胞外Ca 2+。GnRH激动剂刺激可增加GnRH脉冲的幅度，而GnRH拮抗剂治疗可降低GnRH脉冲的幅度。这些结果表明，GnRH受体的表达，GnRH依赖性激活的Ca 2+信号，和GnRH释放的自分泌调节是早期胎儿GnRH神经元的特征，并可能提供一种机制，基因表达和调节胚胎迁移过程中的GnRH分泌。
The characteristic pulsatile secretion of GnRH from hypothalamic neurons is dependent on an autocrine interaction between GnRH and its receptors expressed in GnRH-producing neurons. The ontogeny and function of this autoregulatory process were investigated in studies on the properties of GnRH neurons derived from the olfactory placode of the fetal rat. An analysis of immunocytochemically identified, laser-captured fetal rat hypothalamic GnRH neurons, and olfactory placode-derived GnRH neurons identified by differential interference contrast microscopy, demonstrated coexpression of mRNAs encoding GnRH and its type I receptor. Both placode-derived and immortalized GnRH neurons (GT1-7 cells) exhibited spontaneous electrical activity that was stimulated by GnRH agonist treatment. This evoked response, as well as basal neuronal firing, was abolished by treatment with a GnRH antagonist. GnRH stimulation elicited biphasic intracellular calcium ([Ca2+](i)) responses, and both basal and GnRH-stimulated [Ca2+](i) levels were reduced by antagonist treatment. Perifused cultures released GnRH in a pulsatile manner that was highly dependent on extracellular Ca2+. The amplitude of GnRH pulses was increased by GnRH agonist stimulation and was diminished during GnRH antagonist treatment. These findings demonstrate that expression of GnRH receptor, GnRH-dependent activation of Ca2+ signaling, and autocrine regulation of GnRH release are characteristics of early fetal GnRH neurons and could provide a mechanism for gene expression and regulated GnRH secretion during embryonic migration.