Autoregulation of the androgen receptor at the translational level: Testosterone induces accumulation of androgen receptor mRNA in the rat ventral prostate polyribosomes

Several studies have documented that androgens have the ability to autoregu late their own receptor levels; however, the mechanism of such autoregulati on remains poorly understood. Along these lines, our laboratory has shown t hat testosterone increased androgen receptor (AR) protein levels and bindin g in the castrated rat ventral prostate within 1 h. Ongoing protein synthes is was required for the testosterone effect, as the protein synthesis inhib itor cycloheximide blocked this effect. Testosterone and/or actinomycin D, an mRNA synthesis inhibitor, did not affect the steady-state AR mRNA levels . Therefore, we suggest that the early events induced by testosterone are p osttranscriptional and that protein synthesis is required for the maintenan ce of AR protein and AR mRNA levels. In addition, we hypothesize that the t estosterone posttranscriptional effect is primarily through the sequesterin g of AR mRNA in the prostate polyribosomes. To test this hypothesis, total RNA was isolated from prostate polyribosomes of controls and testosterone-t reated rats and AR mRNA levels were quantitated by competitive reverse tran scription-polymerase chain reaction. Polyribosomes profiles on linear sucro se gradients showed no difference in the sedimentation characteristics of r ibosomal particles from the vehicle-treated control or testosterone-treated animals. Furthermore, because both polyribosomal preparations can direct p rotein synthesis to the same extent in a cell-free system, testosterone doe s not increase the efficiency of translation. However, competitive reverse transcription-polymerase chain reaction revealed that testosterone increase s AR mRNA associated with polyribosomes by threefold after 1 h of treatment compared with control. These data suggest a rapid testosterone-mediated po sttranscriptional mechanism, in which testosterone regulates the stability of the AR mRNA by sequestering it in polyribosomes, and consequently increa sing its translation. (C) 1999 Elsevier Science Inc. All rights reserved.