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

Aging is the greatest risk factor for most chronic diseases. Metabolic dysfunction underlies several chronic diseases, which are further exacerbated by obesity. Dietary interventions can reverse metabolic declines and slow aging processes, although compliance issues remain paramount due to adverse effects on quality of life. 17α-estradiol treatment improves metabolic parameters and slows aging in male mice. The mechanism by which 17α-E2 elicits benefits remain unknown, which has led speculation that an uncharacterized receptor is involved. Herein, we show that 17α-estradiol and 17β-estradiol elicit similar genomic binding and transcriptional activation of ERα and that the ablation of ERα in male mice completely attenuates the beneficial effects of 17α-estradiol. Our findings also suggest that 17α-E2 acts primarily through the liver and/or hypothalamus to elicit benefits, and that 17α-E2 also improves metabolic parameters in male rats. Collectively, these data suggest ERα is a relevant drug target for mitigating chronic diseases in male mammals.

Original languageEnglish (US)
JournalUnknown Journal
DOIs
StatePublished - Jun 3 2020

Keywords

  • 17α-estradiol
  • Aging
  • Estrogen receptor
  • Hypothalamus
  • Liver
  • Metabolism
  • Obesity

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • Immunology and Microbiology(all)
  • Neuroscience(all)
  • Pharmacology, Toxicology and Pharmaceutics(all)

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