IUCT Oncopole, 31100 Toulouse, France.
INSERM-UPS UMR U1048, Institut des Maladies Métaboliques et Cardiovasculaires, Université de Toulouse, BP 84225, CEDEX 04, 31 432 Toulouse, France.
Int J Mol Sci. 2020 Apr 17;21(8):2815. doi: 10.3390/ijms21082815.
Endometriosis is a frequent and chronic inflammatory disease with impacts on reproduction, health and quality of life. This disorder is highly estrogen-dependent and the purpose of hormonal treatments is to decrease the endogenous ovarian production of estrogens. High estrogen production is a consistently observed endocrine feature of endometriosis. mRNA and protein levels of estrogen receptors (ER) are different between a normal healthy endometrium and ectopic/eutopic endometrial lesions: endometriotic stromal cells express extraordinarily higher ERβ and significantly lower ERα levels compared with endometrial stromal cells. Aberrant epigenetic regulation such as DNA methylation in endometriotic cells is associated with the pathogenesis and development of endometriosis. Although there is a large body of data regarding ERs in endometriosis, our understanding of the roles of ERα and ERβ in the pathogenesis of endometriosis remains incomplete. The goal of this review is to provide an overview of the links between endometriosis, ERs and the recent advances of treatment strategies based on ERs modulation. We will also attempt to summarize the current understanding of the molecular and cellular mechanisms of action of ERs and how this could pave the way to new therapeutic strategies.
子宫内膜异位症是一种常见的慢性炎症性疾病,对生殖、健康和生活质量有影响。这种疾病高度依赖雌激素,激素治疗的目的是减少内源性卵巢雌激素的产生。高雌激素产生是子宫内膜异位症中一直观察到的内分泌特征。正常健康的子宫内膜和异位/在位子宫内膜病变之间的雌激素受体(ER)的 mRNA 和蛋白水平不同:与子宫内膜基质细胞相比,子宫内膜异位症基质细胞表达异常高的 ERβ 和显著低的 ERα 水平。子宫内膜异位症细胞中异常的表观遗传调控,如 DNA 甲基化,与子宫内膜异位症的发病机制和发展有关。尽管关于子宫内膜异位症中的 ER 有大量数据,但我们对 ERα 和 ERβ 在子宫内膜异位症发病机制中的作用的理解仍然不完整。本综述的目的是概述子宫内膜异位症、ER 与基于 ER 调节的治疗策略的最新进展之间的联系。我们还将尝试总结 ER 的分子和细胞作用机制的现有理解,以及这如何为新的治疗策略铺平道路。