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. 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 acts primarily 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.
Competing Interest Statement
The authors have declared no competing interest.
Footnotes
Email Addresses of Authors:
Shivani N. Mann shivani-mann{at}ouhsc.edu
Niran Hadad Niran.Hadad{at}jax.org
Molly Nelson-Holte NelsonHolte.Molly{at}mayo.edu
Alicia R. Rothman Alicia-rothman{at}ouhsc.edu
Roshini Sathiaseelan Roshini-sathiaseelan{at}ouhsc.edu
Samim Ali-Mondal Samim-alimondal{at}ouhsc.edu
Martin-Paul Agbaga martin-paul-agbaga{at}ouhsc.edu
Archana Unnikrishnan Archana-Unnikrishnan{at}ouhsc.edu
Subramaniam Malayannan Subramaniam.Malayannan{at}mayo.edu
John Hawse Hawse.John{at}mayo.edu
Derek M. Huffman derek.huffman{at}einstein.yu.edu
Willard M. Freeman bill-freeman{at}omrf.org