Elife 2020 Dec 8;9:e59616
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.
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; and Stout, Michael B, "Health benefits attributed to 17α-estradiol, a lifespan-extending compound, are mediated through estrogen receptor α." (2020). Faculty Research 2020. 252.