HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: 582/1/449    most recent jphysiol.2007.129676v1 Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Roos, S. Articles by Jansson, T. Search for Related Content PubMed PubMed Citation Articles by Roos, S. Articles by Jansson, T. Related Collections Integrative

¹ Perinatal Center, Department of Physiology, Institute of Neuroscience and Physiology, University of Gothenburg, Gothenburg, Sweden
² Department of Obstetrics and Gynecology, University of Cincinnati, College of Medicine, Cincinnati, OH, USA

Pathological fetal growth is associated with perinatal morbidity and the development of diabetes and cardiovascular disease later in life. Placental nutrient transport is a primary determinant of fetal growth. In human intrauterine growth restriction (IUGR) the activity of key placental amino acid transporters, such as systems A and L, is decreased. However the mechanisms regulating placental nutrient transporters are poorly understood. We tested the hypothesis that the mammalian target of rapamycin (mTOR) signalling pathway regulates amino acid transport in the human placenta and that the activity of the placental mTOR pathway is reduced in IUGR. Using immunohistochemistry and culture of trophoblast cells, we show for the first time that the mTOR protein is expressed in the transporting epithelium of the human placenta. We further demonstrate that placental mTOR regulates activity of the L-amino acid transporter, but not system A or taurine transporters, by determining the mediated uptake of isotope-labelled leucine, methylaminoisobutyric acid and taurine in primary villous fragments after inhibition of mTOR using rapamycin. The protein expression of placental phospho-S6K1 (Thr-389), a measure of the activity of the mTOR signalling pathway, was markedly reduced in placentas obtained from pregnancies complicated by IUGR. These data identify mTOR as an important regulator of placental amino acid transport, and provide a mechanism for the changes in placental leucine transport in IUGR previously demonstrated in humans. We propose that mTOR functions as a placental nutrient sensor, matching fetal growth with maternal nutrient availability by regulating placental nutrient transport.

(Received 2 February 2007; accepted after revision 22 April 2007; first published online 26 April 2007)
Corresponding author S. Roos: Perinatal Center, Department of Physiology, Institute of Neuroscience and Physiology, University of Gothenburg, PO Box 432, SE-405 30 Gothenburg, Sweden. Email: sara.roos{at}gu.se

This article has been cited by other articles:

				S. Roos, Y. Kanai, P. D. Prasad, T. L. Powell, and T. Jansson Regulation of placental amino acid transporter activity by mammalian target of rapamycin Am J Physiol Cell Physiol, January 1, 2009; 296(1): C142 - C150. [Abstract] [Full Text] [PDF]