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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...

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Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: eLife Sciences Publications, Ltd 2020
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.
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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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