Autologous regulation of androgen receptor messenger ribonucleic acid in the separate lobes of the rat prostate gland.
Autologous regulation of androgen receptor messenger ribonucleic acid in the separate lobes of the rat prostate gland.
复制标题
大鼠前列腺各叶中雄激素受体信使核糖核酸的自体调节。
DOI：
10.1095/biolreprod53.3.609
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发表时间：
1995
影响因子：
3.6
通讯作者：
Woodham,C
中科院分区：
文献类型：
--
作者：
Prins,GS;Woodham,C
雄激素受体（AR）的差异自调节已经被描述为大鼠前列腺的不同叶。虽然AR在腹侧、背侧和LP1侧叶中受睾酮上调，但LP2侧管上皮细胞在雄激素停用后仍持续表达AR蛋白。为了确定这种差异的自调节机制，本研究检测了大鼠前列腺不同区域AR mRNA的自调节。Northern blot分析显示，雄激素下调了所有前列腺叶中AR mRNA的水平，因为它们的水平在去势后升高，在睾酮替代后下降。原位杂交证实，雄激素停药后AR mRNA水平的增加是由于每个细胞转录物的增加。当与DNA含量归一化时，雄激素停药后AR mRNA的升高是短暂的，3天内腹侧和背叶的AR mRNA水平恢复到控制水平，而侧叶AR信息的升高则延长。定量逆转录-聚合酶链反应研究显示，长期缺乏雄激素时，AR mRNA水平升高仅限于外侧叶LP2管。核运行实验显示，与完整大鼠相比，阉割两天后腹侧、背侧或LP1侧叶的AR基因转录没有变化，这表明转录后机制参与了AR mRNA的自动调节。相比之下，AR基因转录率在外侧LP2管中翻了一番。去势后LP2导管中AR基因转录增加导致AR mRNA水平升高，这可能部分解释了在缺乏睾酮的情况下该区域AR蛋白的持续表达。然而，激素停药后AR翻译与腹侧和背叶AR mRNA水平脱钩的机制尚不清楚。综上所述，目前的数据表明，AR mRNA在大鼠前列腺不同区域的调控存在差异。这些差异可能开始解释不同前列腺叶中AR蛋白的不同自动调节。
Differential autoregulation of androgen receptors (AR) has been previously described for the separate lobes of the rat prostate gland. While AR are up-regulated by testosterone in the ventral, dorsal, and LP1 lateral lobes, the epithelial cells of the LP2 lateral ducts show continued expression of the AR protein following androgen withdrawal. To determine the mechanism of this differential autologous regulation, the present study examined the autoregulation of AR mRNA in the separate regions of the rat prostate gland. Northern blot analysis revealed that AR mRNA levels are down-regulated by androgens in all prostate lobes, since their levels increase following castration and decrease upon testosterone replacement. In situ hybridization confirmed that the increase in AR mRNA levels immediately following androgen withdrawal is due to increased transcripts per cell. When normalized to DNA content, the AR mRNA elevation upon androgen withdrawal was transient, and the value returned to control levels in the ventral and dorsal lobes within three days, while the elevation of AR message in the lateral lobe was prolonged. Quantitative reverse transcriptase-polymerase chain reaction studies revealed that elevated AR mRNA levels in the prolonged absence of androgens were confined to the LP2 ducts of the lateral lobe. Nuclear run-on experiments showed no alteration in AR gene transcription two days after castration in the ventral, dorsal, or LP1 lateral lobes when compared to the values in intact rats, indicating that posttranscriptional mechanisms are involved in AR mRNA autoregulation. In contrast, the AR gene transcription rate doubled in the lateral LP2 ducts. The elevated AR mRNA levels in the LP2 ducts due to increased AR gene transcription following castration may, in part, explain the continued expression of AR protein in that region in the absence of testosterone. However, the mechanism whereby AR translation becomes uncoupled from its AR mRNA levels in the ventral and dorsal lobes after hormone withdrawal remains unclear. In summary, the present data demonstrate that differences exist in AR mRNA regulation within the different regions of the rat prostate gland. These differences may begin to explain differential autoregulation of the AR protein in the separate prostate lobes.