| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Submitted on November 22, 2004
Accepted on March 30, 2005
and 
to Protect Hippocampal Neurons Against Global Ischemia-Induced Cell Death
Dept. of Obstetrics, Gynecology and Women's Health, Division of Reproductive Endocrinology & Infertility; Dept. of Neuroscience; and Dept. of Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx, NY 10461
* To whom correspondence should be addressed. E-mail: etgen{at}aecom.yu.edu.
Estradiol at physiological concentrations intervenes in apoptotic death cascades and ameliorates neuronal death in experimental models of focal and global ischemia. The cellular targets that mediate estradiol protection of hippocampal neurons in global ischemia are, however, unclear. The present study examined the hypothesis that estradiol protects hippocampal neurons in ovariectomized rats via estrogen receptor (ER) 
and/or 
. Estradiol (14 day pretreatment) afforded robust protection of CA1 neurons against global ischemia-induced death. The broad-spectrum ER antagonist ICI 182,780 (intracerebroventricularly, 0 and 12 h after ischemia) abolished estrogen protection, consistent with a role for ERs. To evaluate the potential roles of ER vs. ER in estrogen protection, we administered subtype-selective agonists for 14 days before and 7 days following ischemia. The ER-selective agonist propyl pyrazole triol (PPT, 10 mg/kg) and ER-selective agonist WAY 200070-3 (1 mg/kg) produced nearly complete protection of CA1 neurons in 
50% animals. PPT, but not WAY 200070-3, at doses used for protection, elicited lordosis, negative feedback inhibition of LH release, and reduced weight gain. These findings establish the efficacy of the PPT dose in neuroendocrine assays and specificity of WAY 200070-3 for ER. We also examined the ability of estradiol and neuronal injury to regulate ER and ER expression. Both estradiol and global ischemia markedly increased ER, but not ER, protein in CA1. These data indicate that estradiol can act via ER and ER to protect CA1 neurons from global ischemia-induced death and that both estradiol and global ischemia modulate ER expression in hippocampal CA1.
•
estrogen receptor •
global ischemia •
hippocampus •
ICI 182,780
This article has been cited by other articles:
 |
|
 |
|
  P. D. Alfinito, X. Chen, J. Atherton, S. Cosmi, and D. C. Deecher ICI 182,780 Penetrates Brain and Hypothalamic Tissue and Has Functional Effects in the Brain after Systemic Dosing Endocrinology, October 1, 2008; 149(10): 5219 - 5226. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. M. Wang, L. Liu, and R. D. Brinton Estradiol-17 -Induced Human Neural Progenitor Cell Proliferation Is Mediated by an Estrogen Receptor -Phosphorylated Extracellularly Regulated Kinase Pathway Endocrinology, January 1, 2008; 149(1): 208 - 218. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Jover-Mengual, R. S. Zukin, and A. M. Etgen MAPK Signaling Is Critical to Estradiol Protection of CA1 Neurons in Global Ischemia Endocrinology, March 1, 2007; 148(3): 1131 - 1143. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. A. Harris Estrogen Receptor-{beta}: Recent Lessons from in Vivo Studies Mol. Endocrinol., January 1, 2007; 21(1): 1 - 13. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. Zhao, K. O'Neill, and R. D. Brinton Estrogenic Agonist Activity of ICI 182,780 (Faslodex) in Hippocampal Neurons: Implications for Basic Science Understanding of Estrogen Signaling and Development of Estrogen Modulators with a Dual Therapeutic Profile J. Pharmacol. Exp. Ther., December 1, 2006; 319(3): 1124 - 1132. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
| Endocrinology | Endocrine Reviews | J. Clin. End. & Metab. |
| Molecular Endocrinology | Recent Prog. Horm. Res. | All Endocrine Journals |
