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.
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