1 Perinatal Center, Department of Physiology, Institute of Neuroscience and Physiology, University of Gothenburg, Gothenburg, Sweden; 2 Division of Bio-System Pharmacology, Department of Pharmacology, Graduate School of Medicine, Osaka University, Osaka, Japan; 3 Department of Obstetrics and Gynecology, Medical College of Georgia, Augusta, Georgia; and 4 Department of Obstetrics and Gynecology, University of Cincinnati College of Medicine, Cincinnati, Ohio Submitted 24 June 2008 ; accepted in final form 3 November 2008 The activity of placental amino acid transporters is decreased in intrauterine growth restriction (IUGR), but the underlying regulatory mechanisms have not been established. Inhibition of the mammalian target of rapamycin (mTOR) signaling pathway has been shown to decrease the activity of the system L amino acid transporter in human placental villous fragments, and placental mTOR activity is decreased in IUGR. In the present study, we used cultured primary trophoblast cells to study mTOR regulation of placental amino acid transporters in more detail and to test the hypothesis that mTOR alters amino acid transport activity by changes in transporter expression. Inhibition of mTOR by rapamycin significantly reduced the activity of system A (–17%), system L (–28%), and taurine (–40%) amino acid transporters. mRNA expression of isoforms of the three amino acid transporter systems in response to mTOR inhibition was measured using quantitative real-time PCR. mRNA expression of L -type amino acid transporter 1 (LAT1; a system L isoform) and taurine transporter was reduced by 13% and 50%, respectively; however, mTOR inhibition did not alter the mRNA expression of system A isoforms (sodium-coupled neutral amino acid transporter-1, -2, and -4), LAT2, or 4F2hc. Rapamycin treatment did not significantly affect the protein expression of any of the transporter isoforms. We conclude that mTOR signaling regulates the activity of key placental amino acid transporters and that this effect is not due to a decrease in total protein expression. These data suggest that mTOR regulates placental amino acid transporters by posttranslational modifications or by affecting transporter translocation to the plasma membrane. system A; system L; taurine transporter Address for reprint requests and other correspondence: S. Roos, Perinatal Center, Dept. of Physiology, Institute of Neuroscience and Physiology, Univ. of Gothenburg, PO Box 432, Gothenburg SE-405 30, Sweden (e-mail: sara.roos{at}gu.se )