TESTOSTERONE REGULATES PYRUVATE-DEHYDROGENASE E1-ALPHA IN PROSTATE

The production of enormously high levels of citrate is a major function of the prostate gland. This function is regulated by testosterone. Testosterone stimulates the rate of citrate synthesis by prostate secretory epithelial cells. In order to achieve this effect, testosterone increases the production of oxaloacetate and acetyl CoA which are required for citrate synthesis. A key regulatory step in this metabolic process is the pyruvate dehydrogenase (PDH) reaction which controls the oxidative decarboxylation of pyruvate to acetyl CoA. Previous studies have demonstrated that testosterone stimulates PDH activity of rat ventral prostate (VP). E1 alpha, the oxidative decarboxylation enzyme, is the major regulatory step of the PDH complex. The present studies were initiated to determine if testosterone stimulated the level of E1 alpha in VP epithelial cells. In vivo studies demonstrated that the E1 alpha level of VP was decreased by 24 h castration, and that testosterone administration to castrated rats restored the E1 alpha level. In vitro studies revealed that testosterone (10(-7)-10(-10) M) significantly increased the E1 alpha level of isolated prostate epithelial cells. The increase occurred within 1 h exposure to testosterone. Both cycloheximide and actinomycin suppressed the action of testosterone. This effect of testosterone was tissue-specific in that neither kidney nor liver E1 alpha levels were altered by testosterone treatment. Most importantly, in contrast to VP, testosterone had no effect on the E1 alpha levels of lateral prostate. These results support our proposal that testosterone regulates PDH activity of prostate via a mechanism which involves the regulation of the biosynthesis of E1 alpha.