Alterations in progesterone receptor membrane component 2 (PGRMC2) in the endometrium of macaques afflicted with advanced endometriosis
Alterations in progesterone receptor membrane component 2 (PGRMC2) in the endometrium of macaques afflicted with advanced endometriosis
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DOI：
10.1093/molehr/gas006
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发表时间：
2012-06-01
影响因子：
4
通讯作者：
Slayden, Ov D.
中科院分区：
文献类型：
--
作者：
Keator, Christopher S.;Mah, Kuni;Slayden, Ov D.
猕猴子宫内膜在月经周期中孕激素受体膜成分（PGRMC 1和PGRMC 2）的生殖驱动表达和细胞特异性定位模式尚不清楚。此外，PGRMC 1和PGRMC 2在患有子宫内膜异位症的灵长类动物的分泌性在位子宫内膜中的表达和定位模式也是未知的。因此，我们使用实时PCR来定量PGRMCs在月经周期期间从人工周期猕猴收集的子宫内膜的明确定义的样品中的转录表达水平，以及在患有子宫内膜异位症的自然周期猕猴的分泌期子宫内膜中的转录表达水平。用原位杂交和免疫细胞化学分别对PGRMC 1和PGRMC 2的mRNA和蛋白进行定位。我们比较了PGRMCs的表达和定位模式与核孕酮受体（PGR）的表达和定位模式。PGRMC 1和PGR在周期的增殖期升高，然后在周期的分泌晚期下降到几乎检测不到的水平。PGRMC 2的水平在周期的增殖期最低，然后在分泌期显著增加。PGRMC 2的强染色定位于分泌期的腔上皮和腺上皮。当与人工循环的无病动物相比，患有子宫内膜异位症的猕猴在PGR和PGRMC 1的表达或定位模式方面没有表现出变化，但表现出PGRMC 2转录水平显著降低，PGRMC 2蛋白的细胞内染色模式改变。总的来说，这些结果表明，膜结合的PGRMC 2可以提供一个行动的途径，可能潜在地介导的非基因组的影响，孕酮对腺上皮细胞在分泌期的周期。此外，膜结合的PGRMC 2水平降低可能与常在患有子宫内膜异位症的灵长类动物的子宫内膜中观察到的孕酮不敏感性有关。
The hormonally driven expression and cell-specific localization patterns of the progesterone receptor membrane components (PGRMC1 and PGRMC2) in the macaque endometrium during the menstrual cycle are unknown. Additionally, the expression and localization patterns of PGRMC1 and PGRMC2 in the secretory eutopic endometrium of primates afflicted with endometriosis are also unknown. Therefore, we used real-time PCR to quantify transcript expression levels of the PGRMCs in well-defined samples of endometrium collected from artificially cycled macaques during the menstrual cycle, and in the secretory phase endometrium of naturally cycling macaques afflicted with endometriosis. In situ hybridization and immunocytochemistry were used to localize PGRMC1 and PGRMC2 mRNA and protein, respectively. We compared the patterns of expression and localization of the PGRMCs with the expression and localization patterns of nuclear progesterone receptor (PGR). PGRMC1 and PGR were elevated during the proliferative phases of the cycle, and then declined to nearly undetectable levels during the late secretory phase of the cycle. Levels of PGRMC2 were lowest during the proliferative phases of the cycle and then increased markedly during the secretory phases. Strong staining for PGRMC2 was localized to the luminal and glandular epithelia during the secretory phases. When compared with artificially cycled disease-free animals, macaques with endometriosis exhibited no changes in the expression or localization patterns for PGR and PGRMC1 but exhibited strikingly reduced levels of PGRMC2 transcript and altered intracellular staining patterns for the PGRMC2 protein. Collectively, these results suggest that membrane-bound PGRMC2 may provide a pathway of action that could potentially mediate the non-genomic effects of progesterone on the glandular epithelia during the secretory phase of the cycle. Further, reduced levels of membrane-bound PGRMC2 may be associated with the progesterone insensitivity often observed in the endometrium of primates afflicted with endometriosis.