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 enzy mes in the pathway of citrate production in prostate. Expression of mA AT is modulated by testosterone and prolactin in prostate. We cloned t he promoter and 5'-flanking region of the rat mAAT gene and sequenced 2.0 kilobases of the DNA. This fragment contains the 5'-regulatory pro moter 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 w ith the consensus glucocorticoid response element/androgen response el ement (ARE) and a reported ARE sequence that is different from the con sensus sequence. Functional transcription studies showed that a 481-ba se region containing the two ARE sequences was sufficient for androgen -regulated gene expression. There are multiple transcription start sit es that are regulated by testosterone in prostate. In liver, on the ot her hand, castration did not affect transcription from any of the star t sites. Therefore, these data provide evidence that transcriptional r egulation of the rat pmAAT gene occurs through an ARE located in the 5 '-region. In addition, not only is gene expression modulated by testos terone, but the effect of testosterone on transcription is cell specif ic.