TESTOSTERONE STIMULATES THE BIOSYNTHESIS OF M-ACONITASE AND CITRATE OXIDATION IN PROSTATE EPITHELIAL-CELLS
TESTOSTERONE STIMULATES THE BIOSYNTHESIS OF M-ACONITASE AND CITRATE OXIDATION IN PROSTATE EPITHELIAL-CELLS
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DOI：
10.1016/0303-7207(95)03582-r
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发表时间：
1995-07-01
影响因子：
4.1
通讯作者：
FRANKLIN, RB
中科院分区：
文献类型：
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作者：
COSTELLO, LC;LIU, YY;FRANKLIN, RB
线粒体（m-）顺乌头酸酶是前列腺上皮细胞中的限速调节酶，其使这些细胞的柠檬酸盐氧化最小化。这种独特的代谢特征是前列腺积累和分泌极高水平柠檬酸盐的能力的原因。替吉奥是前列腺生长和功能的主要调节剂，并刺激柠檬酸盐氧化。因此，睾酮的一个重要作用可能是刺激前列腺上皮细胞中的间乌头酸酶。用大鼠腹侧前列腺（VP）上皮细胞进行研究，以确定睾酮对间乌头酸酶水平和相应柠檬酸盐氧化的影响。生理浓度（10（-7）-10（-10）M）的睾酮在体外显著增加新鲜制备的分离的前列腺上皮细胞中的间乌头酸酶水平。这种增加在暴露于激素的3小时内是明显的。睾酮对间乌头酸酶的刺激作用被放线菌素D和放线菌酮所消除。间乌头酸酶的水平和间乌头酸酶活性的水平同样增加睾酮治疗。相应地，睾酮增加了线粒体柠檬酸盐氧化的速率，而对异柠檬酸盐氧化的速率没有影响，从而证明睾酮的作用是专门针对间乌头酸酶反应的。在体内研究表明，去势显着减少和睾酮管理增加前列腺上皮细胞的间乌头酸酶水平。相反，无论是肝脏还是肾脏的间乌头酸酶水平被阉割改变。这些研究表明，睾酮调节前列腺上皮细胞中m-乌头酸酶的生物合成。这似乎是一种细胞特异性效应，因为肾脏和肝脏间乌头酸酶均未受到影响。研究表明，前列腺上皮细胞含有组成和雄激素诱导的m-乌头酸酶成分;而肾脏和肝脏含有组成，但没有雄激素诱导的m-乌头酸酶。与基本上所有其他细胞不同，m-乌头酸酶是前列腺上皮细胞中的调节和受调节的酶。
Mitochondria (m-)aconitase is a rate-limiting regulatory enzyme in prostate epithelial cells which minimizes citrate oxidation by these cells. 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 action of testosterone might be its stimulation of m-aconitase in prostate epithelial cells. Studies were conducted with rat ventral prostate (VP) epithelial cells to establish the effect of testosterone on the level of m-aconitase and corresponding citrate oxidation. Physiological concentrations (10(-7)-10(-10) M) of testosterone in vitro markedly increased the level of m-aconitase in freshly prepared isolated prostate 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 similarly 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-aconitase reaction. In vivo studies revealed that castration markedly decreased and testosterone administration increased the m-aconitase level of prostate epithelial cells. In contrast, neither liver nor kidney m-aconitase level was altered by castration. These studies demonstrate that testosterone regulates the biosynthesis of m-aconitase in prostate epithelial cells. It appears that this is a cell-specific effect since neither kidney nor liver m-aconitase was affected. The studies reveal that prostate epithelial cells contain a constitutive and an androgen-induced m-aconitase component; whereas, kidney and liver contain a constitutive but no androgen-induced m-aconitase. Unlike essentially all other cells, m-aconitase is a regulatory and regulated enzyme in prostate epithelial cells.