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线粒体代谢中的雌激素受体:年龄相关变化及其对妊娠并发症的影响。

Estrogen receptors in mitochondrial metabolism: age-related changes and implications for pregnancy complications.

作者信息

Hinton Antentor, Neikirk Kit, Le Han, Harris Chanel, Oliver Ashton, Martin Pamela, Gaye Amadou

机构信息

Department of Molecular Physiology & Biophysics, Vanderbilt University, Nashville, TN, USA.

Department of Biomedical Sciences, Meharry Medical College, Nashville, TN, USA.

出版信息

Aging Adv. 2024 Dec;1(2):154-171. doi: 10.4103/agingadv.agingadv-d-24-00012. Epub 2024 Dec 20.

Abstract

Estrogen hormones are primarily associated with their role as female sex hormones responsible for primary and secondary sexual development. Estrogen receptors are known to undergo age-dependent decreases due to age-related changes in hormone production. In the mitochondria, estrogen functions by reducing the production of reactive oxygen species in the electron transport chain, inhibiting apoptosis, and regulating mitochondrial DNA content. Moreover, estrogen receptors may be the key components in maintaining mitochondrial membrane potential and structure. Although estrogen plays a crucial role in the development of pregnancy, our understanding of how estrogen receptors change with aging during pregnancy remains limited. During pregnancy, estrogen levels are significantly elevated, with a corresponding upregulation of estrogen receptors, which play various roles in pregnancy. However, the exact role of estrogen receptors in pregnancy complications remains to be further investigated. The paper reviews the role of estrogen receptors in the regulation of mitochondrial metabolism and in pregnancy complications, with a special focus on the effect of age-related changes on estrogen levels and estrogen receptors function. We also address how estrogen maintains mitochondrial function, including reducing the production of reactive oxygen species in the electron transport chain, inhibiting apoptosis, regulating mitochondrial DNA content, and maintaining mitochondrial membrane potential and structure. However, the effects of estrogen on mitochondria-endoplasmic reticulum contacts have not been well studied. Based on these emergent roles in mitochondria, the differential roles of estrogen receptors in pregnancy complications are of great relevance. The paper emphasizes the association between maternal health and estrogen receptors and indicates the need for future research to elucidate the interdependence of estrogen receptor-regulated maternal health with mitochondrial function and their relationship with the gut microbiome. Overall, we summarize the important role of estrogen receptors during pregnancy and highlight the need for further research to better understand the role of estrogen receptors in aging and pregnancy complications. This not only helps to reveal the mechanism underlying the role of estrogen in maternal health but also has potential clinical implications for the development of new therapies targeting age-related diseases and pregnancy complications.

摘要

雌激素主要与其作为负责原发性和继发性性发育的女性性激素的作用相关。已知雌激素受体会因激素产生的年龄相关变化而出现与年龄相关的减少。在线粒体中,雌激素通过减少电子传递链中活性氧的产生、抑制细胞凋亡以及调节线粒体DNA含量来发挥作用。此外,雌激素受体可能是维持线粒体膜电位和结构的关键成分。尽管雌激素在妊娠发育中起着至关重要的作用,但我们对妊娠期间雌激素受体如何随年龄变化的了解仍然有限。在妊娠期间,雌激素水平显著升高,雌激素受体相应上调,其在妊娠中发挥多种作用。然而,雌激素受体在妊娠并发症中的确切作用仍有待进一步研究。本文综述了雌激素受体在调节线粒体代谢和妊娠并发症中的作用,特别关注年龄相关变化对雌激素水平和雌激素受体功能的影响。我们还探讨了雌激素如何维持线粒体功能,包括减少电子传递链中活性氧的产生、抑制细胞凋亡、调节线粒体DNA含量以及维持线粒体膜电位和结构。然而,雌激素对线粒体-内质网接触的影响尚未得到充分研究。基于这些在线粒体中的新出现作用来看,雌激素受体在妊娠并发症中的不同作用具有重要意义。本文强调了母体健康与雌激素受体之间的关联,并指出未来需要开展研究以阐明雌激素受体调节的母体健康与线粒体功能的相互依存关系及其与肠道微生物群的关系。总体而言,我们总结了雌激素受体在妊娠期间的重要作用,并强调需要进一步研究以更好地理解雌激素受体在衰老和妊娠并发症中的作用。这不仅有助于揭示雌激素在母体健康中发挥作用的潜在机制,而且对开发针对年龄相关疾病和妊娠并发症的新疗法具有潜在的临床意义。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/88ee/11748122/483e66f51aca/nihms-2046182-f0001.jpg

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