Citrate accumulation and secretion are primary functions of the prostate glandular epithelium. This function is regulated by testosterone. This relationship is common to human prostate and rat ventral prostate. The latter serves as the experimental model to investigate the metabolic relationships which account for this unique function of prostate as well as the mechanism(s) of action of testosterone. These basic relationships must be elucidated in order to understand the pathological implications in prostate; especially since alterations in citrate production are associated with benign prostatic hypertrophy and with carcinoma of prostate in humans. Furthermore the mechanism of androgenic control of metabolic and related physiological function needs to be understood. This program will continue to elucidate the mechanism by which testosterone regulates mitochondrial aspartate aminotransferase activity which is a specific target for androgenic regulation of prostate citrate production. In addition we will elucidate the two-carbon source of citrate production and then determine the effect of testosterone on this pathway. Ultimately, the question of the total six-carbon precursors of citrate production and secretion and the key mechanisms by which this is regulated by testosterone will be resolved. Once the mechanism of action of testosterone and the metabolic relationships of citrate production have been established in the experimental model, studies of these relationships in human prostate will be feasible.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project (R01)
Project #
5R01DK028015-07
Application #
3228555
Study Section
Reproductive Biology Study Section (REB)
Project Start
1981-07-01
Project End
1990-06-30
Budget Start
1988-04-01
Budget End
1990-06-30
Support Year
7
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, Leslie C; Franklin, Renty B (2012) Cytotoxic/tumor suppressor role of zinc for the treatment of cancer: an enigma and an opportunity. Expert Rev Anticancer Ther 12:121-8
Costello, L C; Franklin, R B; Feng, Pei (2005) Mitochondrial function, zinc, and intermediary metabolism relationships in normal prostate and prostate cancer. Mitochondrion 5:143-53
Costello, L C; Franklin, R B (2002) Testosterone and prolactin regulation of metabolic genes and citrate metabolism of prostate epithelial cells. Horm Metab Res 34:417-24
Costello, L C; Franklin, R B (2000) The intermediary metabolism of the prostate: a key to understanding the pathogenesis and progression of prostate malignancy. Oncology 59:269-82
Costello, L C; Liu, Y; Zou, J et al. (2000) The pyruvate dehydrogenase E1 alpha gene is testosterone and prolactin regulated in prostate epithelial cells. Endocr Res 26:23-39
Liang, J Y; Liu, Y Y; Zou, J et al. (1999) Inhibitory effect of zinc on human prostatic carcinoma cell growth. Prostate 40:200-7
Costello, L C; Franklin, R B; Narayan, P (1999) Citrate in the diagnosis of prostate cancer. Prostate 38:237-45
Costello, L C; Liu, Y; Zou, J et al. (1999) Evidence for a zinc uptake transporter in human prostate cancer cells which is regulated by prolactin and testosterone. J Biol Chem 274:17499-504
Costello, L C; Franklin, R B (1998) Novel role of zinc in the regulation of prostate citrate metabolism and its implications in prostate cancer. Prostate 35:285-96
Costello, L C; Franklin, R B (1997) Citrate metabolism of normal and malignant prostate epithelial cells. Urology 50:3-12

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