Human prostate as will as rat ventral prostate has the unique function of accumulating and secreting extraordinarily high levels of citrate. The source and metabolic. relationships of citrate production by prostate secretory epithelial cells has not been elucidated. The utilization and incorporation of exogenous aspartate is proposed as the major four-carbon source of oxalacetate required for citrate production. This possibility seems most plausible since these cells contain a mitochondrial pathway for transaminating aspartate with net synthesis of citrate, and the aminotransferase is regulated by testosterone. It now becomes essential to elucidate the mechanism(s) by which aspartate is transported from plasma to cytosol against an existing concentration of 60 fold. Therefore, we will determine the presence and characteristics of an aspartate transport mechanism in prostate epithelial cells. Furthermore we will establish that transported aspartate is converted to citrate which is secreted by the prostate. Thereafter we will have a model system for determining the role and effects of testosterone (and other hormones and conditions) in regulating this functional relationship of prostate. In addition these studies will be the forerunner of investigations into the requirements for culturing prostate epithelial cells which retain their normal in situ phenotypic characteristics. Since citrate production is altered in prostate pathology (cancer and hyperplasia), the corresponding metabolic derangements can be studied once these basic relationships are elucidated. The effects of chemotherapeutic agents on these processes can also be studied. Consequently this program will establish needed information for such future application. These studies will involve rat ventral prostate which is analogous to human prostate in regard to metabolic aspects of citrate production. Once these mechanisms are elucidated with ventral prostate, corresponding studies with human prostate epithelium becomes plausible.
