Reproductive Endocrinology Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
Neuroscience Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
Pharmacol Res. 2021 Jan;163:105307. doi: 10.1016/j.phrs.2020.105307. Epub 2020 Nov 25.
Exploring the regulatory effects of estrogen on different body organs via its receptors is largely of interest. Recently, the expression, signaling and the clinical significance of ERα36, the newly identified isoform of ERα, mediating non-genomic signaling of estrogen, have been studied in a wide range of organs and tumors. ERα36 is expressed highly in the CNS and actively involved in neuroprotection. It is also suggested to be an important estrogen receptor involved in preserving bone in postmenopausal women. On the oncological side, although ERα36 has usually been considered to be an oncogenic molecule, results from some studies paradoxically imply its protective role in certain tumors. Collectively, it seems that ERα36 is highly involved in cell type-specific functions of estrogen through its MAPK/ERK signaling, which is dependent on ERα36 expression levels, ligand concentrations and disease stage. The response is also dependent on the levels of ERα66 and ERβ. These factors influence the ERK kinetic and determine the ultimate mitogenic or antimitogenic signaling of estrogen, leading to cell survival or cell death. In this review, we summarize the recent organ-specific, cellular and molecular events and the mechanisms involved in estrogen effects mediated through the ERα36/ ERα66 with a particular focus on carcinomas where more clinical information has recently emerged.
研究雌激素通过其受体对不同身体器官的调节作用具有重要意义。最近，在广泛的器官和肿瘤中研究了 ERα36（新鉴定的 ERα 同工型）的表达、信号转导及其在非基因组雌激素信号转导中的临床意义。ERα36 在中枢神经系统中表达水平较高，积极参与神经保护。它也被认为是参与绝经后妇女保护骨骼的重要雌激素受体。在肿瘤学方面，尽管 ERα36 通常被认为是致癌分子，但一些研究的结果却出人意料地暗示了它在某些肿瘤中的保护作用。总的来说，通过其 MAPK/ERK 信号转导，ERα36 似乎高度参与了雌激素对特定细胞类型的功能，这取决于 ERα36 的表达水平、配体浓度和疾病阶段。这种反应还取决于 ERα66 和 ERβ 的水平。这些因素影响 ERK 的动力学，并决定了雌激素的最终有丝分裂或抗有丝分裂信号，导致细胞存活或细胞死亡。在这篇综述中，我们总结了最近在器官特异性、细胞和分子事件以及通过 ERα36/ERα66 介导的雌激素作用的机制方面的研究进展，特别关注了最近出现更多临床信息的癌。
