Kobayashi Yasuna, Hirokawa Noriko, Ohshiro Naomi, Sekine Takashi, Sasaki Tadanori, Tokuyama Shogo, Endou Hitoshi, Yamamoto Toshinori
Department of Clinical Pharmacy, School of Pharmaceutical Sciences, Showa University, 1-5-8 Hatanodai, Shinagawa-ku, Tokyo 142-8555, Japan.
Biochem Biophys Res Commun. 2002 Jan 11;290(1):482-7. doi: 10.1006/bbrc.2001.6180.
Sex-related differential gene expression of organic anion transporters (rOAT1, rOAT2, and rOAT3) in rat brain, liver, and kidney was investigated. There were no sex differences in the expression of rOAT1 mRNA. rOAT2 mRNA was abundant in the liver and weakly expressed in the kidney of male rats; however, the OAT2 gene was strongly expressed in both organs of females. The abundance of rOAT2 mRNA markedly increased in castrated male rat kidney; however, treatment of castrated male rats with testosterone led to a decrease of rOAT2 mRNA. Expression of rOAT3 mRNA in intact female rats was found in the kidney and brain, whereas in males rOAT3 mRNA was also found in the liver. rOAT3 mRNA markedly decreased in the liver of castrated male rats but increased in testosterone-treated castrated male rats. Moreover, rOAT3 mRNA increased in the hypophysectomized female rat liver, indicating that rOAT3 is an inducible isoform. The present findings suggest that sex steroids play an important role in the expression and maintenance of OAT2/3 isoforms in the rat liver and kidney. Our results provide information on the differential gene expression of OAT isoforms with sex hormone dependency.
研究了大鼠脑、肝和肾中有机阴离子转运体(rOAT1、rOAT2和rOAT3)与性别相关的差异基因表达。rOAT1 mRNA的表达不存在性别差异。rOAT2 mRNA在雄性大鼠肝脏中丰富,在肾脏中弱表达;然而,OAT2基因在雌性大鼠的这两个器官中均强烈表达。去势雄性大鼠肾脏中rOAT2 mRNA的丰度显著增加;然而,用睾酮治疗去势雄性大鼠会导致rOAT2 mRNA减少。在完整雌性大鼠的肾脏和大脑中发现了rOAT3 mRNA的表达,而在雄性大鼠中,rOAT3 mRNA也存在于肝脏中。去势雄性大鼠肝脏中rOAT3 mRNA显著减少,但在睾酮治疗的去势雄性大鼠中增加。此外,垂体切除的雌性大鼠肝脏中rOAT3 mRNA增加,表明rOAT3是一种可诱导的异构体。目前的研究结果表明,性类固醇在大鼠肝脏和肾脏中OAT2/3异构体的表达和维持中起重要作用。我们的结果提供了关于OAT异构体与性激素依赖性差异基因表达的信息。