Regulation of citrate metabolism by androgen in the LNCaP human prostate carcinoma cell line

Abstract

Citrate production and accumulation are characteristic physiological functions of the prostate gland that are regulated by testosterone and prolactin. Results reported here show that treatment of LNCaP cells with dihydrotestosterone (DHT) resulted in increased intracellular citrate and increased citrate accumulation in the medium. Moreover, DHT also caused an increase in both mitochondrial aspartate aminotransferase (mAAT) activity and the steady state level of pmAAT (precursor) mRNA. Androgen treatment increased the rate of citrate oxidation by LNCaP cells as it does in rat ventral prostate which suggests that DHT increased aconitase activity in LNCaP cells. The results reported here are consistent with the operation of the glutamate-aspartate-citrate pathway that we described for rat ventral prostate. In addition, these results provide the first evidence that androgen responsive functions associated with citrate metabolism are retained in LNCaP cells. In addition, and more important, these results suggest that the more aggressive PC-3 carcinoma cell line has a higher rate of citrate oxidation than the less aggressive LNCaP cell line. This could have significant implications for our understanding of the relationship between alterations in prostate citrate metabolism and expression of the malignant phenotype.