Hormone control and expression of androgen receptor coregulator MAGE-11 in human endometrium during the window of receptivity to embryo implantation
Hormone control and expression of androgen receptor coregulator MAGE-11 in human endometrium during the window of receptivity to embryo implantation
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DOI：
10.1093/molehr/gam080
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发表时间：
2008-02-01
影响因子：
4
通讯作者：
Wilson, Elizabeth M.
中科院分区：
文献类型：
--
作者：
Bai, Suxia;Grossman, Gail;Wilson, Elizabeth M.
雄激素受体（AR）是雄性和雌性生殖道的配体激活的转录因子，其活性受辅调节因子结合的调节。最近，我们确定了黑色素瘤抗原基因蛋白-11（法师-11）的MAGEA基因家族，作为一个AR辅调节因子结合AR N-末端FXXLF基序。在这里，我们报告法师-11表达的时间在正常周期的妇女子宫内膜的方式。最高水平的法师-11 mRNA和蛋白质发生在中期分泌阶段，与子宫接受胚胎植入的窗口相一致。对人子宫内膜细胞系的研究以及月经周期的激素分布和周期性子宫内膜中雌激素受体-a表达的模式表明，法师-11 mRNA的升高是由于增殖期雌二醇的下调和分泌早期和中期cAMP信号的上调。与其协同调节功能一致，法师-11与AR定位于分泌中期的腺上皮细胞核中。分泌中期子宫内膜中AR蛋白的增加而AR mRNA的增加表明法师-11稳定腺上皮细胞核中的AR。这得到了低雄激素水平下表达研究的支持，表明AR稳定化依赖于AR N-末端反式激活结构域的法师-11。结果表明，法师-11功能作为一个辅助调节，增加AR转录活性在建立子宫容受性在人类女性。
The androgen receptor (AR) is a ligand-activated transcription factor of the male and female reproductive tracts whose activity is modulated by coregulator binding. We recently identified melanoma antigen gene protein-11 (MAGE-11) of the MAGEA gene family that functions as an AR coregulator by binding the AR N-terminal FXXLF motif. Here we report that MAGE-11 is expressed in a temporal fashion in endometrium of normally cycling women. Highest levels of MAGE-11 mRNA and protein occur in the mid-secretory stage, coincident with the window of uterine receptivity to embryo implantation. Studies in human endometrial cell lines together with the hormone profile of the menstrual cycle and pattern of estrogen receptor-a expression in cycling endometrium suggest the rise in MAGE-11 mRNA results from down-regulation by estradiol during the proliferative phase and up-regulation by cyclic AMP signaling in the early and mid-secretory stage. In agreement with its coregulatory function, MAGE-11 localizes with AR in glandular epithelial cell nuclei in the mid-secretory stage. The increase in AR protein in the mid-secretory endometrium without an increase in AR mRNA suggests MAGE-11 stabilizes AR in glandular epithelial cell nuclei. This was supported by expression studies at low androgen levels indicating AR stabilization by MAGE-11 dependent on the AR N-terminal transactivation domain. The results suggest that MAGE-11 functions as a coregulator that increases AR transcriptional activity during the establishment of uterine receptivity in the human female.