Health benefits attributed to 17α-estradiol, a lifespan-extending compound, are mediated through estrogen receptor α.
Health benefits attributed to 17α-estradiol, a lifespan-extending compound, are mediated through estrogen receptor α.
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归因于17α-雌二醇（一种延伸寿命的化合物）归因于雌激素受体α介导的。
DOI：
10.7554/elife.59616
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发表时间：
2020-12-08
期刊：
影响因子：
7.7
通讯作者：
Stout MB
中科院分区：
文献类型：
--
作者：
Mann SN;Hadad N;Nelson Holte M;Rothman AR;Sathiaseelan R;Ali Mondal S;Agbaga MP;Unnikrishnan A;Subramaniam M;Hawse J;Huffman DM;Freeman WM;Stout MB
代谢功能障碍是几种慢性疾病的基础，其中许多疾病因肥胖而加剧。饮食干预可以扭转代谢衰退和延缓衰老，尽管遵从性问题仍然是最重要的。17α-雌二醇治疗可改善雄性小鼠的代谢参数并延缓衰老。17-α-雌二醇产生这些益处的机制仍未解决。在此，我们发现17α-雌二醇通过雌激素受体α(ERα)引起的基因组结合和转录激活与17β-雌二醇相似。此外，我们还发现，消融ERα可完全减弱17α-E_2对雄性小鼠的有益代谢作用。我们的发现表明，17α-E2可能通过肝脏和下丘脑发挥作用，改善雄性小鼠的代谢参数。最后，我们还确定了17α-E2改善了雄性大鼠的代谢参数，从而证明了17α-E2的有益作用并不局限于小鼠。总而言之，这些研究表明，ERα可能是缓解雄性哺乳动物慢性病的药物靶点。
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.