Abstract

The prostate gland has the unique function of accumulating and secreting high levels of citrate, and testosterone is a major regulator of citrate production by the gland. Citrate production is very high in benign prostate hyperplasia (BPH), and is very low in prostate carcinoma (CA). The proposed studies seek to establish the relationships of hormone regulation of prostate citrate production, to elucidate the mechanisms by which hormones regulate prostatic citrate production, and to apply these insights to address the pathogenesis of BPH and prostatic CA. The two enzymes most directly involved in the regulation of citrate production are mitochondrial aspartate aminotransferase (mAAT) and pyruvate dehydrogenase (PDH). Both enzymes are induced by testosterone. Using rat prostate as the tissue source, the proposed studies will address the role of testosterone in the regulation of the mAAT and PDH E1a genes by characterizing androgen response elements and the factors involved in cell specific response to testosterone in prostate epithelial cells.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project (R01)
Project #
5R01DK028015-14
Application #
2905251
Study Section
Special Emphasis Panel (ZRG2-END (01))
Program Officer
Mullins, Christopher V
Project Start
1981-07-01
Project End
2002-06-30
Budget Start
1999-07-01
Budget End
2002-06-30
Support Year
14
Fiscal Year
1999
Total Cost
Indirect Cost

  Institution

Name
University of Maryland Baltimore
Department
Physiology
Type
Schools of Dentistry
DUNS #
003255213
City
Baltimore
State
MD
Country
United States
Zip Code
21201

  Publications

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

Showing the most recent 10 out of 29 publications