The prostate gland has the unique function of accumulating and secreting extraordinarily high levels of citrate. This function is regulated by testosterone, prolactin, and possibly other hormones. The citrate production is markedly increased prolactin,and possibly other hormones. The citrate production is markedly increased in benign prostatic hyperplasia and is markedly decreased in prostatic carcinoma. The broad objectives are to elucidate the mechanisms of hormonal regulation of prostate citrate production and the hormonal and metabolic transformation associated with prostatic neoplasms. This program is specifically related to the elucidation of the role and mechanism of action of testosterone in regulating prostate citrate production.
One specific aim i s to determine the mechanisms by which testosterone regulates the biosynthesis of mitochondrial aspartate the mechanism by which testosterone regulates the biosynthesis of mitochondrial aspartate aminotransferase (mAAT) a key enzyme in citrate synthesis. The effect of testosterone on transcription of the mAAT gene and on translocation of precursor mAAT into mitochondria will be ascertained. The program also deals with the role and mechanism of action of testosterone in increasing pyruvate oxidation as a source of acetyl coenzyme A for citrate synthesis. The rat ventral prostate is employed as the source of prostate epithelial cells in this study. Ventral prostate, like human prostate, produces high levels of citrate. These studies will set the stage for later studies with human prostate cells, normal and neoplastic.
Showing the most recent 10 out of 29 publications
