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Health benefits attributed to 17α-estradiol, a lifespan-extending compound, are mediated through estrogen receptor α
Metabolic dysfunction underlies several chronic diseases, many of which are exacerbated by obesity. Dietary interventions can reverse metabolic declines and slow aging, although compliance issues remain paramount. 17α-estradiol treatment improves metabolic parameters and slows aging in male mice. Th...
Autores principales: | , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
eLife Sciences Publications, Ltd
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7744101/ https://www.ncbi.nlm.nih.gov/pubmed/33289482 http://dx.doi.org/10.7554/eLife.59616 |
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author | Mann, Shivani N Hadad, Niran Nelson Holte, Molly Rothman, Alicia R Sathiaseelan, Roshini Ali Mondal, Samim Agbaga, Martin-Paul Unnikrishnan, Archana Subramaniam, Malayannan Hawse, John Huffman, Derek M Freeman, Willard M Stout, Michael B |
author_facet | Mann, Shivani N Hadad, Niran Nelson Holte, Molly Rothman, Alicia R Sathiaseelan, Roshini Ali Mondal, Samim Agbaga, Martin-Paul Unnikrishnan, Archana Subramaniam, Malayannan Hawse, John Huffman, Derek M Freeman, Willard M Stout, Michael B |
author_sort | Mann, Shivani N |
collection | PubMed |
description | Metabolic dysfunction underlies several chronic diseases, many of which are exacerbated by obesity. Dietary interventions can reverse metabolic declines and slow aging, although compliance issues remain paramount. 17α-estradiol treatment improves metabolic parameters and slows aging in male mice. The mechanisms by which 17α-estradiol elicits these benefits remain unresolved. Herein, we show that 17α-estradiol elicits similar genomic binding and transcriptional activation through estrogen receptor α (ERα) to that of 17β-estradiol. In addition, we show that the ablation of ERα completely attenuates the beneficial metabolic effects of 17α-E2 in male mice. Our findings suggest that 17α-E2 may act through the liver and hypothalamus to improve metabolic parameters in male mice. Lastly, we also determined that 17α-E2 improves metabolic parameters in male rats, thereby proving that the beneficial effects of 17α-E2 are not limited to mice. Collectively, these studies suggest ERα may be a drug target for mitigating chronic diseases in male mammals. |
format | Online Article Text |
id | pubmed-7744101 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | eLife Sciences Publications, Ltd |
record_format | MEDLINE/PubMed |
spelling | pubmed-77441012020-12-21 Health benefits attributed to 17α-estradiol, a lifespan-extending compound, are mediated through estrogen receptor α Mann, Shivani N Hadad, Niran Nelson Holte, Molly Rothman, Alicia R Sathiaseelan, Roshini Ali Mondal, Samim Agbaga, Martin-Paul Unnikrishnan, Archana Subramaniam, Malayannan Hawse, John Huffman, Derek M Freeman, Willard M Stout, Michael B eLife Medicine Metabolic dysfunction underlies several chronic diseases, many of which are exacerbated by obesity. Dietary interventions can reverse metabolic declines and slow aging, although compliance issues remain paramount. 17α-estradiol treatment improves metabolic parameters and slows aging in male mice. The mechanisms by which 17α-estradiol elicits these benefits remain unresolved. Herein, we show that 17α-estradiol elicits similar genomic binding and transcriptional activation through estrogen receptor α (ERα) to that of 17β-estradiol. In addition, we show that the ablation of ERα completely attenuates the beneficial metabolic effects of 17α-E2 in male mice. Our findings suggest that 17α-E2 may act through the liver and hypothalamus to improve metabolic parameters in male mice. Lastly, we also determined that 17α-E2 improves metabolic parameters in male rats, thereby proving that the beneficial effects of 17α-E2 are not limited to mice. Collectively, these studies suggest ERα may be a drug target for mitigating chronic diseases in male mammals. eLife Sciences Publications, Ltd 2020-12-08 /pmc/articles/PMC7744101/ /pubmed/33289482 http://dx.doi.org/10.7554/eLife.59616 Text en © 2020, Mann et al http://creativecommons.org/licenses/by/4.0/ http://creativecommons.org/licenses/by/4.0/This article is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use and redistribution provided that the original author and source are credited. |
spellingShingle | Medicine Mann, Shivani N Hadad, Niran Nelson Holte, Molly Rothman, Alicia R Sathiaseelan, Roshini Ali Mondal, Samim Agbaga, Martin-Paul Unnikrishnan, Archana Subramaniam, Malayannan Hawse, John Huffman, Derek M Freeman, Willard M Stout, Michael B Health benefits attributed to 17α-estradiol, a lifespan-extending compound, are mediated through estrogen receptor α |
title | Health benefits attributed to 17α-estradiol, a lifespan-extending compound, are mediated through estrogen receptor α |
title_full | Health benefits attributed to 17α-estradiol, a lifespan-extending compound, are mediated through estrogen receptor α |
title_fullStr | Health benefits attributed to 17α-estradiol, a lifespan-extending compound, are mediated through estrogen receptor α |
title_full_unstemmed | Health benefits attributed to 17α-estradiol, a lifespan-extending compound, are mediated through estrogen receptor α |
title_short | Health benefits attributed to 17α-estradiol, a lifespan-extending compound, are mediated through estrogen receptor α |
title_sort | health benefits attributed to 17α-estradiol, a lifespan-extending compound, are mediated through estrogen receptor α |
topic | Medicine |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7744101/ https://www.ncbi.nlm.nih.gov/pubmed/33289482 http://dx.doi.org/10.7554/eLife.59616 |
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