PMID- 12564383
OWN - NLM
STAT- MEDLINE
DCOM- 20030321
LR  - 20191106
IS  - 0161-813X (Print)
IS  - 0161-813X (Linking)
VI  - 24
IP  - 1
DP  - 2003 Jan
TI  - Estradiol enhances the neurotoxicity of glutamate in GT1-7 cells through an 
      estrogen receptor-dependent mechanism.
PG  - 65-73
AB  - Glutamate plays an important role in neuroendocrine regulation of reproduction 
      through acting on the N-methyl-D-asparate receptor (NMDAR) in the preoptic area 
      (POA). However, a larger dose of glutamate is neurotoxic. Estradiol (E2) 
      increases the responsiveness of neurons to glutamate through activation and/or 
      expression of NMDAR. In order to investigate whether estradiol modulates the 
      neurotoxic effect of glutamate on the neurons through estrogen receptor (ER), 
      immortalized GT1-7 cells, which simultaneously express ER and NMDAR were used. 
      Tamoxifen and ICI 182,780, ER antagonist, were used to investigate whether the ER 
      is involved in the effect of estradiol on glutamate-induced neurotoxicity. 
      MK-801, a NMDAR antagonist, was used to confirm the enhancement of NMDAR-mediated 
      neurotoxicity by estradiol. Neurotoxicity was evaluated by cell viability and LDH 
      efflux. Cell death was observed by flow cytometry and DNA fragmentation. The 
      results showed that: (1) estradiol (10 nM, incubated for 3 days) significantly 
      enhanced the glutamate-induced neuronal death; (2) the percentages of necrosis 
      and apoptosis were elevated after glutamate treatment, and estradiol 
      significantly enhanced the glutamate-induced cell death; (3) glutamate-induced 
      DNA fragmentation was enhanced by E2-pretreatment; (4) the induction of cell 
      death and increase of LDH efflux after glutamate treatment were also enhanced by 
      E2-pretreatment; (5) both the tamoxifen and ICI 182,780 abolished the 
      estradiol-enhanced NMDAR expression and neurotoxicity of glutamate; (6) higher 
      dose of MK-801 (2 microM) was needed in E2-pretreated cells than in 
      non-E2-pretreated group to block the glutamate-induced neurotoxicity. These 
      results suggested that pretreatment of estradiol might enhance the expression of 
      NMDAR and subsequent glutamate-induced neurotoxicity on the GT1-7 cells through 
      an ER-dependent manner.
FAU - Yang, Rei-Cheng
AU  - Yang RC
AD  - Department of Physiology, Kaohsiung Medical University, No. 100, Shih-Chuan 1st 
      Road, Kaohsiung 807, Taiwan, ROC.
FAU - Shih, Huei-Chuan
AU  - Shih HC
FAU - Hsu, Hseng-Kuang
AU  - Hsu HK
FAU - Chang, Hwei-Chiu
AU  - Chang HC
FAU - Hsu, Chin
AU  - Hsu C
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - Netherlands
TA  - Neurotoxicology
JT  - Neurotoxicology
JID - 7905589
RN  - 0 (Receptors, Estrogen)
RN  - 0 (Receptors, N-Methyl-D-Aspartate)
RN  - 3KX376GY7L (Glutamic Acid)
RN  - 4TI98Z838E (Estradiol)
SB  - IM
MH  - Animals
MH  - Apoptosis/drug effects/physiology
MH  - Cell Line
MH  - Drug Synergism
MH  - Estradiol/*toxicity
MH  - Glutamic Acid/*toxicity
MH  - Mice
MH  - Neurons/drug effects/metabolism/pathology
MH  - Receptors, Estrogen/*metabolism
MH  - Receptors, N-Methyl-D-Aspartate/metabolism
EDAT- 2003/02/05 04:00
MHDA- 2003/03/22 04:00
CRDT- 2003/02/05 04:00
PHST- 2003/02/05 04:00 [pubmed]
PHST- 2003/03/22 04:00 [medline]
PHST- 2003/02/05 04:00 [entrez]
AID - S0161-813X(02)00108-0 [pii]
AID - 10.1016/s0161-813x(02)00108-0 [doi]
PST - ppublish
SO  - Neurotoxicology. 2003 Jan;24(1):65-73. doi: 10.1016/s0161-813x(02)00108-0.