Bailey J D, Centers A, Jennes L
Department of Anatomy and Neurobiology, University of Kentucky College of Medicine, Lexington, KY 40536, USA.
J Neuroendocrinol. 2006 Jan;18(1):1-12. doi: 10.1111/j.1365-2826.2005.01361.x.
Glutamate provides excitatory input to gonadotrophin-releasing hormone (GnRH) neurones and elicits a response indicative of AMPA receptors. To determine if and which AMPA subunits are expressed by GnRH neurones, we conducted triple-label immunohistochemistry and confocal analyses on tissue obtained at 08.00, 12.00, 16.00 and 20.00 h from young and middle-aged, persistently oestrous (MA-PE) rats that were ovariectomised and primed with oestrogen and progesterone to induce a luteinising hormone (LH) surge. Each AMPA subunit was found in GnRH neurones, but in different patterns across the diurnal cycle, which were influenced by age. GluR1 expression increased earlier in young rats and the percentage of Fos-positive GnRH neurones expressing GluR1 rose significantly and was sustained from 12.00-16.00 h. GluR1 expression was delayed in MA-PE rats and the percentage of Fos-positive GnRH neurones expressing GluR1 peaked at 20.00 h. GluR2 expression in GnRH neurones did not change over time and was not affected by age; however, the percentage of Fos-positive GnRH neurones expressing GluR2 increased earlier and was sustained from 08.00-16.00 h in young rats whereas, in MA-PE rats, this percentage peaked at 20.00 h. GluR3 expression also increased earlier in young rats and peaked at 12.00 h but was delayed in MA-PE rats and peaked at 20.00 h. The number of Fos-positive GnRH neurones that coexpressed GluR3 peaked at 12.00 h in young rats but showed little change from 12.00-20.00 h in MA-PE rats. GluR4 expression was maintained at higher levels at 08.00 and 12.00 h in young rats; although the percentage of Fos-positive GnRH neurones expressing GluR4 peaked at 12.00 h in young rats, it showed little change in MA-PE rats. In summary, our data show that a higher proportion of Fos-positive GnRH neurones coexpressed AMPA receptor subunits in young rats and the expression, particularly of GluR1 and GluR2, was increased and sustained throughout the surge, whereas GluR3 and GluR4 expression peaked just before. In MA-PE rats, the rate of expression of GluR subunits and Fos in GnRH neurones was altered in a manner that may explain the delay and attenuation of the LH surge.
谷氨酸为促性腺激素释放激素（GnRH）神经元提供兴奋性输入，并引发一种表明存在α-氨基-3-羟基-5-甲基-4-异恶唑丙酸（AMPA）受体的反应。为了确定GnRH神经元是否表达以及表达哪些AMPA亚基，我们对从年轻和中年、持续发情（MA-PE）的大鼠身上获取的组织进行了三重标记免疫组织化学和共聚焦分析，这些大鼠已接受卵巢切除术并用雌激素和孕酮预处理以诱导促黄体生成素（LH）激增，取材时间分别为08:00、12:00、16:00和20:00。在GnRH神经元中发现了每个AMPA亚基，但在昼夜周期中呈现不同模式，且受年龄影响。GluR1在年轻大鼠中表达增加得更早，表达GluR1的Fos阳性GnRH神经元百分比显著上升，并在12:00至16:00持续存在。在MA-PE大鼠中GluR1表达延迟，表达GluR1的Fos阳性GnRH神经元百分比在20:00达到峰值。GnRH神经元中GluR2的表达不随时间变化且不受年龄影响；然而，表达GluR2的Fos阳性GnRH神经元百分比在年轻大鼠中更早增加并在08:00至16:00持续存在，而在MA-PE大鼠中，该百分比在20:00达到峰值。GluR3在年轻大鼠中表达也更早增加并在12:00达到峰值，但在MA-PE大鼠中延迟并在20:00达到峰值。共表达GluR3的Fos阳性GnRH神经元数量在年轻大鼠中于12:00达到峰值，但在MA-PE大鼠中从12:00至20:00变化不大。在年轻大鼠中，GluR4在08:00和12:00保持较高水平；尽管表达GluR4的Fos阳性GnRH神经元百分比在年轻大鼠中于12:00达到峰值，但在MA-PE大鼠中变化不大。总之，我们的数据表明，在年轻大鼠中，更高比例的Fos阳性GnRH神经元共表达AMPA受体亚基，并且其表达，特别是GluR1和GluR2的表达，在整个激增过程中增加并持续，而GluR3和GluR4的表达在激增前达到峰值。在MA-PE大鼠中，GnRH神经元中GluR亚基和Fos的表达速率发生改变，这可能解释了LH激增的延迟和减弱。
