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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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Detalles Bibliográficos
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
Descripción
Sumario: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.