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.

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Research Project (R01)
Project #
2R01HD016193-04A2
Application #
3313497
Study Section
Reproductive Endocrinology Study Section (REN)
Project Start
1982-08-01
Project End
1990-11-30
Budget Start
1987-12-01
Budget End
1988-11-30
Support Year
4
Fiscal Year
1988
Total Cost
Indirect Cost
Name
University of Maryland Baltimore
Department
Type
Schools of Dentistry/Oral Hygn
DUNS #
003255213
City
Baltimore
State
MD
Country
United States
Zip Code
21201
Costello, L C; Franklin, R B (1994) Effect of prolactin on the prostate. Prostate 24:162-6
Lao, L; Franklin, R B; Costello, L C (1993) High-affinity L-aspartate transporter in prostate epithelial cells that is regulated by testosterone. Prostate 22:53-63
Costello, L C; Lao, L; Franklin, R (1993) Citrate modulation of high-affinity aspartate transport in prostate epithelial cells. Cell Mol Biol (Noisy-le-grand) 39:515-24
Costello, L C; Franklin, R B (1991) Concepts of citrate production and secretion by prostate: 2. Hormonal relationships in normal and neoplastic prostate. Prostate 19:181-205
Costello, L C; Franklin, R B (1991) Concepts of citrate production and secretion by prostate. 1. Metabolic relationships. Prostate 18:25-46
Franklin, R B; Lao, L X; Costello, L C (1990) Evidence for two aspartate transport systems in prostate epithelial cells. Prostate 16:137-45
Costello, L C; Akuffo, V; Franklin, R B (1988) Net citrate production by isolated prostate epithelial cells. Enzyme 39:125-33
Costello, L C; Khan, M A; Franklin, R B (1988) Preliminary studies on the cultivation and characterization of mini-pig prostate epithelial cells. Cell Biol Int Rep 12:637-46
Franklin, R B; Kukoyi, B I; Akuffo, V et al. (1987) Testosterone stimulation of mitochondrial aspartate aminotransferase levels and biosynthesis in rat ventral prostate. J Steroid Biochem 28:247-56
Franklin, R B; Kahng, M W; Akuffo, V et al. (1986) The effect of testosterone on citrate synthesis and citrate oxidation and a proposed mechanism for regulation of net citrate production in prostate. Horm Metab Res 18:177-81