Mutual antagonism of estrogen receptors α and β and their preferred interactions with steroid receptor coactivators in human osteoblastic cell lines
Mutual antagonism of estrogen receptors α and β and their preferred interactions with steroid receptor coactivators in human osteoblastic cell lines
复制标题
DOI：
10.1677/joe.0.1760349
复制
发表时间：
2003-03-01
影响因子：
4
通讯作者：
Spelsberg, TC
中科院分区：
文献类型：
--
作者：
Monroe, DG;Johnsen, SA;Spelsberg, TC
雌激素是一种主要的性类固醇，影响骨骼的生长、维持和体内平衡。雌激素受体的两种亚型（ER α和ER β）介导雌激素的转录作用。尽管ER的两种亚型在一些人成骨细胞（OB）细胞系中存在并发挥作用，但ER α和ER β同源或异源二聚体对转录的差异调节很少。这份报告表明，ER α和ER β共表达降低转录能力（相对于每个ER亚型单独）的雌激素反应元件依赖性报告基因在OBs，但不是在其他非成骨细胞系。这些数据表明，ER α和ER β共表达可以差异影响某些细胞类型的转录激活程度。有趣的是，类固醇激素受体共激活因子-1（SRC 1）的过表达导致ERP以及共表达ER α和ER β的优先转录增强，而SRC 2的过表达似乎优先增强ER α反式激活。SRC 3过表达未能增强雌激素依赖性转录的任何Ek的组合在OBs. Similar过表达实验在COS 7细胞表现出优先增强Ek α功能与所有SRC，包括SRC 3。我们的数据还表明，SRC 3 mRNA在成骨细胞中减少，表明SRC 3可能在这些细胞中仅起次要作用。这些数据表明，各种ER亚型的反式激活能力是SRC物种和细胞类型依赖性的。
Estrogen is a major sex steroid that affects the growth, maintenance, and homeostasis of the skeleton. Two isoforms of the estrogen receptor (ERalpha and ERbeta) mediate the transcriptional effects of estrogen. Although both isoforms of ER are present and functional in some human osteoblast (OB) cell lines, there is minimal iriformation on the differential regulation of transcription by ERalpha and ERbeta homo- or heterodimers. This report demonstrates that ERalpha and ERbeta coexpression decreases the transcriptional capacity (relative to each ER isoform alone) on an estrogen response element-dependent reporter gene in OBs but not in other non-osteoblastic cell lines. These data suggest that ERalpha and ERbeta coexpression can differentially influence the degree of transcriptional activation in certain cell types. Interestingly, the overexpression of the steroid hormone receptor coactivator-1 (SRC 1) resulted in preferential transcriptional enhancement by ERP as well as coexpressed ERalpha and ERbeta, whereas SRC2 overexpression appeared to preferentially enhance ERa transactivation. SRC3 overexpression failed to enhance estrogen-dependent transcription of any Ek combination in OBs. Similar overexpression experiments in COS7 cells exhibited preferential enhancement of Ekalpha function with all SRCs, including SRC3. Our data also demonstrated that SRC3 mRNA is reduced in ostcoblastic cells, suggesting that SRC3 may have only a minor role in these cells. These data suggest that the transactivation capacity of various ER isoforms is both SRC species and cell type dependent.