David Geffen School of Medicine, Department of Medicine, Division of Endocrinology, Diabetes, and Hypertension, University of California, Los Angeles, California.
Iris Cantor-UCLA Women's Health Research Center, University of California, Los Angeles, California.
Endocrinology. 2020 Feb 1;161(2). doi: 10.1210/endocr/bqz017.
The incidence of chronic disease is elevated in women after menopause. Increased expression of ESR1 (the gene that encodes the estrogen receptor alpha, ERα) in muscle is highly associated with metabolic health and insulin sensitivity. Moreover, reduced muscle expression levels of ESR1 are observed in women, men, and animals presenting clinical features of the metabolic syndrome (MetSyn). Considering that metabolic dysfunction elevates chronic disease risk, including type 2 diabetes, heart disease, and certain cancers, treatment strategies to combat metabolic dysfunction and associated pathologies are desperately needed. This review will provide published work supporting a critical and protective role for skeletal muscle ERα in the regulation of mitochondrial function, metabolic homeostasis, and insulin action. We will provide evidence that muscle-selective targeting of ERα may be effective for the preservation of mitochondrial and metabolic health. Collectively published findings support a compelling role for ERα in the control of muscle metabolism via its regulation of mitochondrial function and quality control. Studies identifying ERα-regulated pathways essential for disease prevention will lay the important foundation for the design of novel therapeutics to improve metabolic health of women while limiting secondary complications that have historically plagued traditional hormone replacement interventions.
绝经后女性慢性疾病的发病率升高。肌肉中 ESR1（编码雌激素受体 alpha，ERα 的基因）表达增加与代谢健康和胰岛素敏感性高度相关。此外，患有代谢综合征（MetSyn）临床特征的女性、男性和动物的肌肉 ESR1 表达水平降低。考虑到代谢功能障碍会增加慢性疾病的风险，包括 2 型糖尿病、心脏病和某些癌症，因此迫切需要治疗策略来对抗代谢功能障碍和相关的病理。本综述将提供支持骨骼肌 ERα 在调节线粒体功能、代谢稳态和胰岛素作用中的关键和保护作用的已发表研究工作。我们将提供证据表明，肌肉特异性靶向 ERα 可能有效保护线粒体和代谢健康。已发表的研究结果共同支持 ERα 通过调节线粒体功能和质量控制来控制肌肉代谢的作用。确定 ERα 调节的对疾病预防至关重要的途径的研究将为设计新型治疗方法奠定重要基础，这些方法可改善女性的代谢健康，同时限制传统激素替代干预措施历来存在的继发性并发症。
