The synthetic estrogen 4-estren-3α,17β-diol (estren) induces estrogen-like neuroprotection
Estrogen has demonstrated neuroprotective properties, which may underlie the observed preventive effect of estrogen-based hormone therapy (HT) against the development of neurodegenerative disorders such as Alzheimer's disease. Deleterious side effects of HT have increased efforts to develop saf...
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doaj-8371580c44b94d3f80fffb7d08728b592021-03-20T04:50:54ZengElsevierNeurobiology of Disease1095-953X2005-06-01191331339The synthetic estrogen 4-estren-3α,17β-diol (estren) induces estrogen-like neuroprotectionMyriam Cordey0Usha Gundimeda1Rayudu Gopalakrishna2Christian J. Pike3Neuroscience Graduate Program, University of Southern California, Los Angeles, CA 90089, USA; Andrus Gerontology Center, University of Southern California, Los Angeles, CA 90089, USAKeck School of Medicine, Department of Cell and Neurobiology, University of Southern California, Los Angeles, CA 90089, USAKeck School of Medicine, Department of Cell and Neurobiology, University of Southern California, Los Angeles, CA 90089, USANeuroscience Graduate Program, University of Southern California, Los Angeles, CA 90089, USA; Andrus Gerontology Center, University of Southern California, Los Angeles, CA 90089, USA; Corresponding author. Andrus Gerontology Center, University of Southern California, 3715 McClintock Avenue, Los Angeles, CA 90089-0191, USA. Fax: +1 213 740 4787.Estrogen has demonstrated neuroprotective properties, which may underlie the observed preventive effect of estrogen-based hormone therapy (HT) against the development of neurodegenerative disorders such as Alzheimer's disease. Deleterious side effects of HT have increased efforts to develop safer compounds that selectively reproduce beneficial estrogen actions. Recently, 4-estren-3α,17β-diol (estren) was identified as having estrogen agonist properties in bone, without significantly stimulating growth of reproductive tissues. Here, we examined whether estren parallels the neuroprotective actions of estrogen against β-amyloid (Aβ) in cultured cerebrocortical neurons. Estren increased neuronal viability to a similar extent to that observed with 17β-estradiol (E2) and 17α-estradiol. As we previously reported for E2, estren rapidly increased PKC activity, and PKC inhibition prevented estren neuroprotection. In contrast, the estrogen receptor antagonist ICI 182,780 blocked E2, but not estren neuroprotection. Our results indicate that estren-induced activation of rapid cell signaling pathways protects cultured neurons from Aβ toxicity.http://www.sciencedirect.com/science/article/pii/S09699961050002644-Estren-3α, 17β-DiolEstrenEstrogen17β-Estradiol17α-Estradiolβ-Amyloid |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Myriam Cordey Usha Gundimeda Rayudu Gopalakrishna Christian J. Pike |
spellingShingle |
Myriam Cordey Usha Gundimeda Rayudu Gopalakrishna Christian J. Pike The synthetic estrogen 4-estren-3α,17β-diol (estren) induces estrogen-like neuroprotection Neurobiology of Disease 4-Estren-3α, 17β-Diol Estren Estrogen 17β-Estradiol 17α-Estradiol β-Amyloid |
author_facet |
Myriam Cordey Usha Gundimeda Rayudu Gopalakrishna Christian J. Pike |
author_sort |
Myriam Cordey |
title |
The synthetic estrogen 4-estren-3α,17β-diol (estren) induces estrogen-like neuroprotection |
title_short |
The synthetic estrogen 4-estren-3α,17β-diol (estren) induces estrogen-like neuroprotection |
title_full |
The synthetic estrogen 4-estren-3α,17β-diol (estren) induces estrogen-like neuroprotection |
title_fullStr |
The synthetic estrogen 4-estren-3α,17β-diol (estren) induces estrogen-like neuroprotection |
title_full_unstemmed |
The synthetic estrogen 4-estren-3α,17β-diol (estren) induces estrogen-like neuroprotection |
title_sort |
synthetic estrogen 4-estren-3α,17β-diol (estren) induces estrogen-like neuroprotection |
publisher |
Elsevier |
series |
Neurobiology of Disease |
issn |
1095-953X |
publishDate |
2005-06-01 |
description |
Estrogen has demonstrated neuroprotective properties, which may underlie the observed preventive effect of estrogen-based hormone therapy (HT) against the development of neurodegenerative disorders such as Alzheimer's disease. Deleterious side effects of HT have increased efforts to develop safer compounds that selectively reproduce beneficial estrogen actions. Recently, 4-estren-3α,17β-diol (estren) was identified as having estrogen agonist properties in bone, without significantly stimulating growth of reproductive tissues. Here, we examined whether estren parallels the neuroprotective actions of estrogen against β-amyloid (Aβ) in cultured cerebrocortical neurons. Estren increased neuronal viability to a similar extent to that observed with 17β-estradiol (E2) and 17α-estradiol. As we previously reported for E2, estren rapidly increased PKC activity, and PKC inhibition prevented estren neuroprotection. In contrast, the estrogen receptor antagonist ICI 182,780 blocked E2, but not estren neuroprotection. Our results indicate that estren-induced activation of rapid cell signaling pathways protects cultured neurons from Aβ toxicity. |
topic |
4-Estren-3α, 17β-Diol Estren Estrogen 17β-Estradiol 17α-Estradiol β-Amyloid |
url |
http://www.sciencedirect.com/science/article/pii/S0969996105000264 |
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