Prins G S, Woodham C
Department of Obstetrics and Gynecology, Michael Reese Hospital, University of Illinois College of Medicine, Chicago 60616, USA.
Biol Reprod. 1995 Sep;53(3):609-19. doi: 10.1095/biolreprod53.3.609.
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.
先前已描述了大鼠前列腺不同叶中雄激素受体（AR）的差异自调节。在腹叶、背叶和LP1侧叶中，AR受睾酮上调，而在雄激素撤除后，LP2侧叶导管的上皮细胞仍持续表达AR蛋白。为了确定这种差异自调节的机制，本研究检测了大鼠前列腺不同区域中AR mRNA的自调节。Northern印迹分析显示，雄激素在所有前列腺叶中均下调AR mRNA水平，因为去势后其水平升高，而睾酮替代后则降低。原位杂交证实，雄激素撤除后AR mRNA水平立即升高是由于每个细胞的转录本增加。以DNA含量进行标准化后，雄激素撤除后AR mRNA的升高是短暂的，腹叶和背叶中的值在三天内恢复到对照水平，而侧叶中AR信息的升高则持续时间更长。定量逆转录-聚合酶链反应研究表明，在长期缺乏雄激素的情况下，AR mRNA水平升高仅限于侧叶的LP2导管。核转录实验显示，与完整大鼠相比，去势两天后腹叶、背叶或LP1侧叶中AR基因转录无变化，表明转录后机制参与了AR mRNA的自调节。相反，LP2侧叶导管中的AR基因转录率增加了一倍。去势后由于AR基因转录增加导致LP2导管中AR mRNA水平升高，这可能部分解释了在无睾酮的情况下该区域中AR蛋白的持续表达。然而，激素撤除后腹叶和背叶中AR翻译与其AR mRNA水平解偶联的机制仍不清楚。总之，目前的数据表明，大鼠前列腺不同区域中AR mRNA调节存在差异。这些差异可能开始解释不同前列腺叶中AR蛋白的差异自调节。
