Androgen Regulation of Androgen Receptor Messenger Ribonucleic Acid Differs in Rat Prostate and Selected Brain Areas

Abstract

Androgens bind to specific high-affinity receptors (AR), thereby initiating gene transcription. We investigated the effects of testosterone (T), dihydrotestosterone (DHT), and 17β-estradiol (E2) on AR transcription and binding in prostate, medial basal hypothalamus (MBH), preoptic area (POA), amygdala, hippocampus, and cortex in the rat. Androgen receptor mRNA was measured by a ribonuclease protection assay. Cytosolic and nuclear AR binding (ARc and ARn, respectively) were measured by in vitro binding assays. In the prostate AR mRNA levels were low in intact animals. Castration produced a fourfold elevation of AR mRNA which was reduced to intact values by treatment with T or DHT (P < 0.05; n = 4). E2 had no effect compared to castrate levels. In contrast to the prostate, no treatment effect was observed on the expression of AR gene in the MBH, POA, amygdala, hippocampus, or cortex. On the premise that treatment effects on AR mRNA in the brain may require longer than 48 h, we treated rats for 4 and 7 days and found no treatment effect on the expression of AR mRNA in MBH, POA, or amygdala. Next, we compared AR binding with its mRNA between prostate and various brain areas. Castration significantly increased ARc and reduced ARn compared to intact levels, and androgen treatments restored both ARc and ARn to intact values in prostate and brain areas (P < 0.05; n = 5). Changes in AR mRNA levels in prostate corresponded to changes in ARc but not ARn in castrated and androgen-treated males, which suggests that ARc is newly synthesized receptor. In contrast, ARc differed quantitatively between prostate and neural tissues. These results show that DHT regulates AR transcription in rat prostate as effectively as T. Our data also suggest that AR gene transcriptional activity in prostate and selected brain areas may be subjected to differential regulatory mechanisms. This may be due to the presence of tissue-specific regulatory proteins.