@article{7fd8b49b8b58461096a7d49a8b47c67f,
title = "Health benefits attributed to 17α- estradiol, a lifespan-extending compound, are mediated through estrogen receptor α",
abstract = "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. 17a-estradiol treatment improves metabolic parameters and slows aging in male mice. The mechanisms by which 17a-estradiol elicits these benefits remain unresolved. Herein, we show that 17a-estradiol elicits similar genomic binding and transcriptional activation through estrogen receptor a (ERa) to that of 17b-estradiol. In addition, we show that the ablation of ERa completely attenuates the beneficial metabolic effects of 17a-E2 in male mice. Our findings suggest that 17a-E2 may act through the liver and hypothalamus to improve metabolic parameters in male mice. Lastly, we also determined that 17a-E2 improves metabolic parameters in male rats, thereby proving that the beneficial effects of 17a-E2 are not limited to mice. Collectively, these studies suggest ERa may be a drug target for mitigating chronic diseases in male mammals.",
author = "Mann, {Shivani N.} and Niran Hadad and Holte, {Molly Nelson} and Rothman, {Alicia R.} and Roshini Sathiaseelan and Mondal, {Samim Ali} and Agbaga, {Martin Paul} and Archana Unnikrishnan and Malayannan Subramaniam and John Hawse and Huffman, {Derek M.} and Freeman, {Willard M.} and Stout, {Michael B.}",
note = "Funding Information: National Institutes of HealthR00 AG51661 Michael B Stout Harold Hamm Diabetes CenterPilot Research Funding Shivani N Mann Michael B Stout National Institutes of HealthR01 AG069742 Michael B Stout National Institutes of HealthR01 AG059430 Willard M Freeman Veterans Affairs Oklahoma CityI01BX003906 Willard M Freeman University of Oklahoma Health Sciences CenterP30 EY012190 Martin-Paul Agbaga National Institutes of HealthR01 EY030513 Martin-Paul Agbaga National Institutes of HealthT32 AG052363 Shivani N Mann Einstein Nathan Shock CenterP30 AG038072 Michael B Stout. Funding Information: We thank Dr. Kenneth Korach at the National Institute of Environmental Health Sciences for providing ERa KO and WT littermate mice. We also thank Dr. Lora Bailey-Downs, Richard Brush, and Michael Sullivan for technical support. This work was supported by the National Institutes of Health (R00 AG51661 and R01 AG069742 to MBS, T32 AG052363 to SNM, R01 EY030513 to M-PA, and R01 AG059430 to WMF), Veterans Affairs (I01B ⨯ 003906 to WMF) and pilot research funding from the Harold Hamm Diabetes Center (MBS and SNM), Einstein Nathan Shock Center (P30 AG038072) of Excellence in the Basic Biology of Aging (MBS), and OUHSC Lipidomics Core (P30 EY012190).",
year = "2020",
month = dec,
doi = "10.7554/eLife.59616",
language = "English (US)",
volume = "9",
pages = "1--30",
journal = "eLife",
issn = "2050-084X",
publisher = "eLife Sciences Publications",
}