Document Detail


Equine estrogens differentially prevent neuronal cell death induced by glutamate.
MedLine Citation:
PMID:  12853093     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
OBJECTIVE: In the present study, neuronal PC12 cells and hippocampal HT22 cells maintained in culture were used to test the neuroprotective effect of equine estrogens estrone, 17beta-estradiol, 17alpha-estradiol, equilin, 17beta-dihydroequilin, 17alpha-dihydroequilin, equilenin, 17beta-dihydroequilenin, 17alpha-dihydroequilenin, Delta(8)-estrone(,) and Delta(8),17beta-estradiol against glutamate toxicity. METHODS: The HT22 and PC12 cells were grown in Dulbecco modified Eagle medium supplemented with 5% horse serum, 10% fetal bovine serum, and 10 mM HEPES. The undifferentiated PC12 cells were plated on collagen-coated, 96-well plastic plates at 10,000 cells per well, and the HT22 cells were plated on uncoated 96-well plates at 2500 cells per well. Twenty-four hours after plating, various concentrations of estrogens (0.1-40 microM) and glutamate (1-10 mM) were added in a total volume of 100 microL. After 24 hours, cell viability was determined using the MTS cell proliferation assay. Results were verified in some experiments by using the lactate dehydrogenase cytotoxicity assay. RESULTS: The results indicate that cell toxicity in both cell lines was directly proportional to the concentration of glutamate. The lowest dose of glutamate that reduced cell viability by 50% under these conditions was 1.8 mM for HT22 cells and 3 mM for PC12 cells. All estrogens tested were neuroprotective against glutamate-induced cell death in a typical dose-related manner. However, these estrogens differed extensively with respect to their neuroprotective potencies. In both cell lines, the Delta(8)-ring B unsaturated estrogens were the most neuroprotective, whereas the classic estrogens 17beta-estradiol, estrone, and 17alpha-estradiol were the least potent. The order of potency was Delta(8),17beta-estradiol > Delta(8)-estrone > 17beta-dihydroequilenin > 17alpha-dihydroequilenin > equilenin > 17beta-dihydroequilin = equilin > 17alpha-dihydroequilin > 17beta-estradiol > estrone > 17alpha-estradiol in PC12 cells and Delta(8),17beta-estradiol > Delta(8)-estrone > equilenin = 17beta-dihydroequilenin > 17beta-dihydroequilin > equilin > 17alpha-dihydroequilenin > 17alpha-dihydroequilin > 17alpha-estradiol = 17beta-estradiol > estrone in HT22 cells. CONCLUSIONS: Our data indicate that the neurotoxic effects of glutamate can be inhibited differentially by various equine estrogens. The less estrogenic (uterotropic) Delta(8) estrogens were the most effective neuroprotectors, and further chemical modifications of these estrogens may provide compounds that are useful for preventing neurodegenerative diseases in both women and men.
Authors:
Bhagu R Bhavnani; Mauricio Berco; Julie Binkley
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Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Journal of the Society for Gynecologic Investigation     Volume:  10     ISSN:  1071-5576     ISO Abbreviation:  J. Soc. Gynecol. Investig.     Publication Date:  2003 Jul 
Date Detail:
Created Date:  2003-07-10     Completed Date:  2004-03-19     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  9433806     Medline TA:  J Soc Gynecol Investig     Country:  United States    
Other Details:
Languages:  eng     Pagination:  302-8     Citation Subset:  IM    
Affiliation:
Department of Obstetrics and Gynecology, Institute of Medical Sciences, University of Toronto, and St. Michael's Hospital, Toronto, Ontario, Canada.
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MeSH Terms
Descriptor/Qualifier:
Animals
Cell Line
Dose-Response Relationship, Drug
Equilenin / pharmacology
Equilin / analogs & derivatives*,  pharmacology
Estradiol / pharmacology
Estradiol Congeners / chemistry,  pharmacology*
Estrone / pharmacology
Glutamic Acid / pharmacology*
Hippocampus
Neurons / drug effects*
Neuroprotective Agents / pharmacology*
PC12 Cells
Rats
Structure-Activity Relationship
Chemical
Reg. No./Substance:
0/Estradiol Congeners; 0/Neuroprotective Agents; 474-86-2/Equilin; 50-28-2/Estradiol; 517-09-9/Equilenin; 53-16-7/Estrone; 56-86-0/Glutamic Acid; 651-55-8/dihydroequilin

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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