Autologous regulation of androgen receptor messenger ribonucleic acid in the separate lobes of the rat prostate gland.

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.