AUTOLOGOUS REGULATION OF ANDROGEN RECEPTOR MESSENGER-RIBONUCLEIC-ACIDIN THE SEPARATE LOBES OF THE RAT PROSTATE-GLAND

Differential autoregulation of androgen receptors (AR) has been previo usly described for the separate lobes of the rat prostate gland. While AR are up-regulated by testosterone in the ventral, dorsal, and LP1 l ateral lobes, the epithelial cells of the LP2 lateral ducts show conti nued expression of the AR protein following androgen withdrawal. To de termine the mechanism of this differential autologous regulation, the present study examined the autoregulation of AR mRNA in the separate r egions of the rat prostate gland, Northern blot analysis revealed that AR mRNA levels are down-regulated by androgens in all prostate robes, since their levels increase following castration and decrease upon te stosterone replacement. In situ hybridization confirmed that the incre ase in AR mRNA levels immediately following androgen withdrawal is due to increased transcripts per cell. When normalized to DNA content, th e AR mRNA elevation upon androgen withdrawal was transient, and the va lue 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 reactio n studies revealed that elevated AR mRNA levels in the prolonged absen ce of androgens were confined to the LP2 ducts of the lateral lobe. Nu clear run-on experiments showed no alteration in AR gene transcription two days after castration in the ventral, dorsal, or LP1 lateral lobe s when compared to the values in intact rats, indicating that posttran scriptional mechanisms are involved in AR mRNA autoregulation. In cont rast, 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 continue d expression of AR protein in that region in the absence of testostero ne. However, the mechanism whereby AR translation becomes uncoupled fr om its AR mRNA levels in the ventral and dorsal lobes after hormone wi thdrawal remains unclear. In summary, the present data demonstrate tha t differences exist in AR mRNA regulation within the different regions of the rat prostate gland. These differences may begin to explain dif ferential autoregulation of the AR protein in the separate prostate lo bes.