Effects of aging on N-methyl-D-aspartate (NMDA)-induced GnRH and LH release in female rats
Effects of aging on N-methyl-D-aspartate (NMDA)-induced GnRH and LH release in female rats
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DOI：
10.1016/s0006-8993(96)00862-1
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发表时间：
1996-11-18
期刊：
影响因子：
2.9
通讯作者：
Moguilevsky, JA
中科院分区：
文献类型：
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作者：
Arias, P;Carbone, S;Moguilevsky, JA
为了评估下丘脑-垂体-卵巢系统的变化是否涉及兴奋性氨基酸神经传递对GnRH神经元的调节作用的改变，这些变化诱导衰老期间生育能力的降低和性周期的改变。本研究测定了NMDA对去势老龄大鼠（15月龄）和幼龄大鼠（90日龄）下丘脑前视区和内侧基底区（APOA-MBH）促性腺激素释放激素（GnRH）释放的影响。在第二系列实验中，还测定了老年和年轻去势雌性大鼠对下丘脑内（推拉）给予NMDA的体内LH释放反应。在孵育期间，在老年和年轻大鼠中观察到相似的基础GnRH释放速率。向培养基中添加NMDA显著增加了两组的GnRH释放;然而，老年大鼠对NMDA的GnRH释放反应（P < 0.01）显著低于年轻大鼠（年轻：基础：50 +/- 10; NMDA 15 '：410 +/- 63。22，5 '：1，469 +/- 300;老年：基础：47 +/- 10; NMDA 15'：210 +/- 30; 22，5 '：350 +/- 65 ng/GnRH/mg。蛋白质）。在整个体内实验中测量的LH水平表明，基础LH浓度显着低于老年组。平均LH浓度（组分1至6）在老年组中显著较低（年轻组：3.9 +/- 0.07，老年组：2.4 +/- 0.03 ng/ml，P < 0.01）。下丘脑注射谷氨酸激动剂后10分钟，老年大鼠对NMDA的LH释放反应（4.2 ± 1.6ng/ml）显著低于年轻大鼠（18.0 ± 6.1ng/ml; P < 0.05）。年轻大鼠的LH水平增加到580%，而在老年大鼠中，与先前的基础值相比仅为47%。总之，目前的结果表明，GnRH对NMDA神经传递的反应。对GnRH神经元具有主要兴奋作用的兴奋性输入在老年大鼠中显著减少，这些数据进一步支持了这一假设，即对GnRH神经元的兴奋性输入的减少可能直接参与了在衰老过程中观察到的下丘脑-垂体-卵巢轴活动的减少。
In order to evaluate if the changes of the hypothalamic-pituitary-ovary asis that induce a decrease in fertility and modifications in the sexual cycles during senescence involve modifications in the regulatory action of excitatory amino acid neurotransmission on GnRH neurons. we measured the in vitro effects of NMDA on GnRH release by the anterior preoptic and medial basal hypothalamic areas (APOA-MBH) of castrated aging (Is months old) and young (90 days of age) rats. In a second series of experiments the in vivo LH release response to intrahypothalamic (push-pull) administration of NMDA to aged and young castrated female rats was also determined. A similar rate of basal GnRH release was observed in old and young rats during the incubation time. The addition of NMDA to the medium significantly increased GnRH release in both groups; nevertheless, the GnRH release response to NMDA was significantly lower in old (P < 0.01) than in young rats (Young: Basal: 50 +/- 10; NMDA 15': 410 +/- 63. 22,5': 1,469 +/- 300; Old: Basal: 47 +/- 10; NMDA 15':210 +/- 30; 22,5': 350 +/- 65 ng/GnRH/mg . protein). The LH levels measured throughout the in vivo experiments indicated that basal LH concentrations were significantly lower in the aged group. The mean LH concentrations (fractions 1 to 6) was significantly lower in the aged group (Young: 3.9 +/- 0.07, Old: 2.4 +/- 0.03 ng/ml, P < 0.01). The LH release response to NMDA measured 10 min after the intrahypothalamic administration of the glutamate agonist uas significantly lower in aged rats (4.2 +/- 1.6 ng/ml) as compared to young animals (18.0 +/- 6.1 ng/ml; P < 0.05). LH levels in young rats increased to 580% vs., and only 47% in aged rats as compared to previous basal values. In conclusion, present results demonstrate that the GnRH responses to NMDA neurotransmission. which has a predominantly excitatory effects on GnRH neurons, is significantly decreased in old rats, these data give further support to the hypothesis that a decrease in the excitatory inputs to GnRH neurons could be directly involved in the reduction of the hypothalamic-pituitary-ovary axis activity observed during aging.