TESTOSTERONE STIMULATES THE BIOSYNTHESIS OF M-ACONITASE AND CITRATE OXIDATION IN PROSTATE EPITHELIAL-CELLS

Mitochondria (m-)aconitase is a rate-limiting regulatory enzyme in pro state epithelial cells which minimizes citrate oxidation by these cell s. This unique metabolic characteristic is responsible for the ability of the prostate to accumulate and secrete extraordinarily high levels of citrate. Testosterone is a major regulator of prostate growth and function, and stimulates citrate oxidation. Therefore, an important ac tion of testosterone might be its stimulation of m-aconitase in prosta te epithelial cells. Studies were conducted with rat ventral prostate (VP) epithelial cells to establish the effect of testosterone on the l evel of m-aconitase and corresponding citrate oxidation. Physiological concentrations (10(-7)-10(-10) M) of testosterone in vitro markedly i ncreased the level of m-aconitase in freshly prepared isolated prostat e epithelial cells. This increase was apparent within 3 h of exposure to the hormone. The stimulatory effect of testosterone on m-aconitase was abolished by actinomycin D and by cycloheximide. Both the level of m-aconitase enzyme and the level of m-aconitase activity were similar ly increased by testosterone treatment. Correspondingly, testosterone increased the rate of mitochondrial citrate oxidation while having no effect on the rate of isocitrate oxidation, thereby demonstrating that the action of testosterone is specifically targeted at the m-aconitas e reaction. In vivo studies revealed that castration markedly decrease d and testosterone administration increased the m-aconitase level of p rostate epithelial cells. In contrast, neither liver nor kidney m-acon itase level was altered by castration. These studies demonstrate that testosterone regulates the biosynthesis of m-aconitase in prostate epi thelial cells. It appears that this is a cell-specific effect since ne ither kidney nor liver m-aconitase was affected. The studies reveal th at prostate epithelial cells contain a constitutive and an androgen-in duced m-aconitase component; whereas, kidney and liver contain a const itutive but no androgen-induced m-aconitase. Unlike essentially all ot her cells, m-aconitase is a regulatory and regulated enzyme in prostat e epithelial cells.