Estradiol selectively regulates agonist binding sites on the N-methyl-D-aspartate receptor complex in the CA1 region of the hippocampus.
Estradiol selectively regulates agonist binding sites on the N-methyl-D-aspartate receptor complex in the CA1 region of the hippocampus.
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DOI：
10.1210/endo.131.2.1353442
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发表时间：
1992-08
期刊：
影响因子：
4.8
通讯作者：
N. Weiland
中科院分区：
文献类型：
--
作者：
N. Weiland
雌激素改变认知功能，降低女性和实验室动物癫痫发作的阈值。这两种活动都受到海马体中兴奋性神经递质谷氨酸的调节。为了评估雌二醇通过增加谷氨酸结合位点来增加海马对谷氨酸激活的敏感性的假设，测量了海马中N-甲基-D-天冬氨酸（NMDA）激动剂位点的密度。（由NMDA取代的谷氨酸决定），竞争性拮抗剂位点（CGP 39653）、非竞争性拮抗剂位点（MK 801）以及红藻氨酸和AMPA的非NMDA谷氨酸受体（分别使用红藻氨酸盐和CNQX）使用放射自显影程序测量。两天的雌二醇治疗增加密度的NMDA受体激动剂，但不是竞争性或非竞争性NMDA受体拮抗剂结合位点专门在海马CA 1区。非竞争性NMDA拮抗剂位点的密度，但是，雌二醇治疗的齿状回下降。卵巢类固醇对海马任何区域的红藻氨酸或AMPA受体的密度没有影响。这些数据表明，NMDA受体/离子通道复合物上的激动剂和拮抗剂结合位点由尚未鉴定的机制独立调节，并且这种调节在海马中具有区域特异性。卵巢激素治疗的NMDA激动剂位点的增加应导致海马对谷氨酸激活的敏感性增加，这可能介导雌二醇对学习和癫痫发作活动的一些影响。
Estradiol alters cognitive function and lowers the threshold for seizures in women and laboratory animals. Both of these activities are modulated by the excitatory neurotransmitter glutamate in the hippocampus. To assess the hypothesis that estradiol increases the sensitivity of the hippocampus to glutamate activation by increasing glutamate binding sites, the densities of N-methyl-D-aspartate (NMDA) agonist sites (determined by NMDA displaced glutamate), competitive antagonist sites (CGP 39653), noncompetitive antagonist sites (MK801) as well as the non-NMDA glutamate receptors for kainate and AMPA (using kainate and CNQX, respectively) were measured using autoradiographic procedures. Two days of estradiol treatment increased the density of NMDA agonist, but not of competitive nor noncompetitive NMDA antagonist binding sites exclusively in the CA1 region of the hippocampus. The density of noncompetitive NMDA antagonist sites, however, was decreased in the dentate gyrus by estradiol treatment. Ovarian steroids had no effect on the density of kainate or AMPA receptors in any region of the hippocampus examined. These data indicate that the agonist and antagonist binding sites on the NMDA receptor/ion channel complex are regulated independently by an as yet unidentified mechanism, and that this regulation exhibits regional specificity in the hippocampus. The increase in NMDA agonist sites with ovarian hormone treatment should result in an increase in the sensitivity of the hippocampus to glutamate activation which may mediate some of the effects of estradiol on learning and epileptic seizure activity.