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首页> 外文期刊>Journal of Cellular Physiology >Regulation of multidrug resistance gene mdr1b/mdr1 expression in isolated mouse uterine epithelial cells.
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Regulation of multidrug resistance gene mdr1b/mdr1 expression in isolated mouse uterine epithelial cells.

机译：多药耐药性基因的调控mdr1b /凋亡表达在孤立的小鼠子宫上皮细胞。

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摘要

The mammalian uterine epithelium (UE) undergoes drastic physiological and morphological changes during pregnancy. Steady-state levels of murine mdr1b mRNA, transcribed from a multidrug resistance gene encoding a membrane protein which functions as a transporter of lipophilic cytotoxic agents, are low in nonpregnant, cycling UE, but drastically increase (about 1,500- to 2,000-fold) at day 8 of gestation. At day 16 of gestation, levels of mdr1b mRNA are 2,500- to 3,000-fold higher than those in the cycling UE cells. Levels of mdr1b mRNA were elevated to levels comparable to those observed during pregnancy, in the UE of ovariectomized mice following 5-8 days of estrogen and progesterone administration. Withdrawal of these hormones resulted in a drastic reduction of mdr1b mRNA within 36 hr. These results suggested that steroid hormones alone can account for increased mdr1b mRNA expression and do not require the presence of other placenta/embryo-derived factors. Moreover, the hormonal effect on uterine mdr1b mRNA biosynthesis during pregnancy apparently is a delayed phenomenon. Nuclear run-on assays demonstrated that the rate of mdr1b transcription in UE cells prepared from 15-day pregnant mice (d-15 UE cells) was about two- to three-fold higher than that in nonpregnant UE cells. This increased transcription rate alone cannot account for mdr1b mRNA accumulation during pregnancy. mdr1b mRNA expression was investigated in primary cultures of d-15 UE cells. mdr1b mRNA levels decayed by 50% within 3-4 hr of culture and reached a steady-state 0.5-2% of initial levels by 24 hr. The rate of mdr1b mRNA decay in primary d-15 UE cells was decreased by treatment with alpha-amanitin or cycloheximide, suggesting that the decay pathway requires both transcription and de novo protein synthesis. Our results suggest that multiple mechanisms are involved in the maintenance of the high levels of mdr1b mRNA in pregnant UE cells. Furthermore, these data suggest that increased mRNA stability may contribute to the accumulation ofmdr1b transcript during pregnancy.
机译：哺乳动物子宫上皮(问题)的经历剧烈的生理和形态变化在怀孕期间。从多种mdr1b mRNA,转录耐药基因编码一个膜蛋白函数作为一种亲脂性的运输车细胞毒性剂、低妊娠的,骑自行车问题,但大幅增加(大约1500年2000倍)在妊娠的第八天。妊娠,mdr1b mRNA水平2500 -3000倍高于循环问题细胞。期间观察到的水平相当怀孕,在切除卵巢的老鼠的问题后5 - 8天的雌激素和孕激素管理。导致mdr1b mRNA的急剧下降在36小时。类固醇激素可以独自占增加mdr1b mRNA表达和不需要的其他胎盘/ embryo-derived的存在的因素。怀孕期间mdr1b信使rna生物合成显然是一个延迟的现象。加添的化验证明mdr1b的速率问题细胞转录从15天准备怀孕的老鼠(d-15问题细胞)两到3倍高于妊娠的问题细胞。不能占mdr1b mRNA在积累怀孕。在初级文化d-15问题细胞。在3 - 4人力资源文化水平的50%和达到稳态0.5初始的-2%24小时。主要d-15问题细胞减少了治疗蝇蕈素与之一或环己酰亚胺,暗示衰变路径需要转录和蛋白质合成新创。结果表明,多个机制参与高水平的维修mdr1b mRNA在怀孕问题细胞。这些数据表明,增加mRNA的稳定性可能导致积累ofmdr1b吗怀孕期间成绩单。

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