Ebling F J, Alexander I H, Urbanski H F, Hastings M H
Department of Anatomy, University of Cambridge, UK.
J Neuroendocrinol. 1995 Jul;7(7):555-66. doi: 10.1111/j.1365-2826.1995.tb00792.x.
Siberian hamsters (Phodopus sungorus) transferred from stimulatory photoperiods (long days: LD) to inhibitory photoperiods (short days: SD) undergo testicular regression within 8 weeks. This reproductive response to photoperiod was blocked by systemic daily treatment with the glutamatergic agonist N-methyl-D-aspartate (NMDA: 20 mg/kg BW, sc). This powerful effect of NMDA demonstrates the potential for endogenous glutamate to regulate reproductive function. The overall aim of the subsequent studies was to investigate the site and mechanism of action of this glutamatergic agonist in order to identify potential mechanisms through which endogenous glutamate might act. To investigate whether the effect of systemic NMDA was via an effect on the circadian timing system, alterations in gonadal regression and recrudescence, seasonal coat changes (pelage) and body weight (BW) were examined. It would be predicted that long-term cycles of all these seasonal parameters would be affected if the action of NMDA were to perturb the transduction of photoperiodic information. Daily treatments with NMDA, which initially maintained reproductive function in hamsters exposed to SD, did not influence the time course of subsequent testicular recrudescence, nor did they influence long-term cycles of pelage and BW. Moreover, treatment with NMDA induced a dose-dependent increase in serum concentrations of LH within 15 min of systemic injection. These data are consistent with the hypothesis that systemic NMDA exerts it reproductive effects not via an action on the circadian system, but via an action on secretion of GnRH. To investigate potential central sites of action of glutamate, induction of the immediate early gene c-fos, an acute marker of cellular response, was evaluated immunocytochemically (ICC) in brain areas after treatment with NMDA. Although dual-label ICC studies revealed that NMDA did not induce c-fos within GnRH neurons, NMDA did induce c-fos in many cells in the region of the organum vasculosum of the lamina terminalis (OVLT), an area containing a large number of GnRH perikarya, and in the arcuate nucleus, a region close to GnRH secretory terminals in the median eminence. The lack of c-fos induction of GnRH cells argues against a direct effect of NMDA on GnRH neurons. Thus, we examined immunocytochemically the distribution of the common NMDAR1 glutamate receptor subunit to evaluate further the potential sites of glutamatergic action. As expected, NMDAR1-ir was widespread in perikarya throughout the brain, including the region of the OVLT and the arcuate nucleus.(ABSTRACT TRUNCATED AT 400 WORDS)
从刺激性光周期（长日照：LD）转移至抑制性光周期（短日照：SD）的西伯利亚仓鼠（Phodopus sungorus），在8周内会出现睾丸退化。对光周期的这种生殖反应，可通过每天全身性给予谷氨酸能激动剂N - 甲基 - D - 天冬氨酸（NMDA：20 mg/kg体重，皮下注射）来阻断。NMDA的这种强大作用表明内源性谷氨酸具有调节生殖功能的潜力。后续研究的总体目标是探究这种谷氨酸能激动剂的作用位点和作用机制，以确定内源性谷氨酸可能发挥作用的潜在机制。为了研究全身性NMDA的作用是否是通过影响昼夜节律系统，我们检测了性腺退化和再生、季节性换毛（被毛）及体重（BW）的变化。如果NMDA的作用干扰了光周期信息的转导，那么预计所有这些季节性参数的长期周期都会受到影响。每天用NMDA处理，最初可维持暴露于短日照下仓鼠的生殖功能，但并不影响随后睾丸再生的时间进程，也不影响被毛和体重的长期周期。此外，全身性注射NMDA后15分钟内，其处理可使血清促黄体生成素（LH）浓度呈剂量依赖性增加。这些数据与以下假设一致：全身性NMDA并非通过作用于昼夜节律系统发挥其生殖作用，而是通过作用于促性腺激素释放激素（GnRH）的分泌来发挥作用。为了探究谷氨酸潜在的中枢作用位点，在用NMDA处理后，通过免疫细胞化学（ICC）评估了即时早期基因c - fos的诱导情况，c - fos是细胞反应的急性标志物。尽管双重标记ICC研究显示NMDA并未在GnRH神经元内诱导c - fos表达，但NMDA确实在终板血管器（OVLT）区域的许多细胞中诱导了c - fos表达，OVLT区域含有大量GnRH核周体，并且在弓状核中也有诱导，弓状核是靠近正中隆起处GnRH分泌终末的区域。GnRH细胞缺乏c - fos诱导表明NMDA对GnRH神经元没有直接作用。因此，我们通过免疫细胞化学方法检测了常见的NMDAR1谷氨酸受体亚基分布，以进一步评估谷氨酸能作用的潜在位点。正如预期的那样，NMDAR1免疫反应性广泛分布于整个大脑的核周体中，包括OVLT区域和弓状核。（摘要截选至400字）
