ANDROGEN MODULATION OF MULTIPLE TRANSCRIPTION START SITES OF THE MITOCHONDRIAL ASPARTATE-AMINOTRANSFERASE GENE IN RAT PROSTATE

Mitochondrial aspartate aminotransferase (mAAT) is one of two key enzymes in the pathway of citrate production in prostate. Expression of mAAT is modulated by testosterone and prolactin in prostate. We cloned the promoter and 5'-flanking region of the rat mAAT gene and sequenced 2.0 kilobases of the DNA. This fragment contains the 5'-regulatory promoter region that lacks a TATA and a CCAAT box but is G+C rich. The 5'-upstream flanking region contains sequences that have high homology with the consensus glucocorticoid response element/androgen response element (ARE) and a reported ARE sequence that is different from the consensus sequence. Functional transcription studies showed that a 481-base region containing the two ARE sequences was sufficient for androgen-regulated gene expression. There are multiple transcription start sites that are regulated by testosterone in prostate. In liver, on the other hand, castration did not affect transcription from any of the start sites. Therefore, these data provide evidence that transcriptional regulation of the rat pmAAT gene occurs through an ARE located in the 5'-region. In addition, not only is gene expression modulated by testosterone, but the effect of testosterone on transcription is cell specific.