Endogenously expressed estrogen receptors mediate neuroprotection in hippocampal cells (HT22) |
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Authors: | Deecher Darlene C Daoud Pamela Bhat Ramesh A O'Connor Lawrence T |
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Affiliation: | Women's Health Research Institute, Wyeth Research, Collegeville, Pennsylvania 19426, USA. deeched@wyeth.com |
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Abstract: | Discovery of estrogen receptors (ER) in the central nervous system and the ability of estrogens to modulate neural circuitry and act as neurotrophic factors, suggest a therapeutic role of this steroid. To gain better understanding of the specificity and cellular mechanisms involved in estrogen-mediated neuroprotection, a mouse hippocampal neuronal cell line (HT22) was evaluated. Earlier reports indicated this cell line was devoid of ERs. Contrary to these findings, characterization of HT22 cells using RT-PCR, immunoblot, immunocytochemical, and radioligand binding techniques revealed endogenous expression of ER. The predominant subtype appeared to be ERalpha with functional activity confirmed using an ERE-tk-luciferase assay. The ability of an ER antagonist, ICI-182780, to block the neuroprotective effects of estrogens confirmed ER was involved mechanistically in neuroprotection. In conclusion, HT22 cells express functional ERalpha or a closely related ER enabling this cell line to be used to profile estrogens for neuroprotective properties acting via an ER-dependent mechanism. |
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Keywords: | estrogen receptors genomic neuronal estrogen responsive element |
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