Health benefits attributed to 17α- estradiol, a lifespan-extending compound, are mediated through estrogen receptor α

Shivani N. Mann, Niran Hadad, Molly Nelson Holte, Alicia R. Rothman, Roshini Sathiaseelan, Samim Ali Mondal, Martin Paul Agbaga, Archana Unnikrishnan, Malayannan Subramaniam, John Hawse, Derek M. Huffman, Willard M. Freeman, Michael B. Stout

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish (US)
Article numbere59616
Pages (from-to)1-30
Number of pages30
JournaleLife
Volume9
DOIs
StatePublished - Dec 2020

ASJC Scopus subject areas

  • Neuroscience(all)
  • Immunology and Microbiology(all)
  • Biochemistry, Genetics and Molecular Biology(all)

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