PMID- 21285325
OWN - NLM
STAT- MEDLINE
DCOM- 20110427
LR  - 20211203
IS  - 1945-7170 (Electronic)
IS  - 0013-7227 (Print)
IS  - 0013-7227 (Linking)
VI  - 152
IP  - 3
DP  - 2011 Mar
TI  - Maternal protein restriction in the rat inhibits placental insulin, mTOR, and 
      STAT3 signaling and down-regulates placental amino acid transporters.
PG  - 1119-29
LID - 10.1210/en.2010-1153 [doi]
AB  - The mechanisms underlying reduced fetal growth in response to maternal protein 
      restriction are not well established. Maternal levels of insulin, IGF-I, and 
      leptin are decreased in rats fed a low protein (LP) diet. Because these hormones 
      stimulate placental amino acid transporters in vitro, we hypothesized that 
      maternal protein restriction inhibits placental leptin, insulin/IGF-I, and 
      mammalian target of rapamycin signaling and down-regulates the expression and 
      activity of placental amino acid transporters. Pregnant rats were fed either an 
      isocaloric low protein (LP, 4% protein) or control diet (18% protein) and studied 
      at gestational day (GD)15, GD19, or GD21 (term 23). At GD19 and GD21, placental 
      expression of phosphorylated eukaryotic initiation factor 4E binding protein 1 
      (Thr-36/46 or Thr-70) and phosphorylated S6 ribosomal protein (Ser-235/236) was 
      decreased in the LP group. In addition, placental expression of phosphorylated S6 
      kinase 1 (Thr-389), phosphorylated Akt (Thr-308), and phosphorylated signal 
      transducer and activator of transcription 3 (Tyr-705) was reduced at GD21. In 
      microvillous plasma membranes (MVM) isolated from placentas of LP animals, 
      protein expression of the sodium-coupled neutral amino acid transporter (SNAT)2 
      and the large neutral amino acid transporters 1 and 2 was reduced at GD19 and 
      GD21. MVM SNAT1 protein expression was reduced at GD21 in LP rats. SNAT4 and 4F2 
      heavy chain expression in MVM was unaltered. System A and L amino acid 
      transporter activity was decreased in MVM from LP animals at GD19 and GD21. In 
      conclusion, maternal protein restriction inhibits placental insulin, mammalian 
      target of rapamycin signaling, and signal transducer and activator of 
      transcription 3 signaling, which is associated with a down-regulation of 
      placental amino acid transporters. We speculate that maternal endocrine and 
      metabolic control of placental nutrient transport reduces fetal growth in 
      response to protein restriction.
FAU - Rosario, Fredrick J
AU  - Rosario FJ
AD  - Center for Pregnancy and Newborn Research, Department of Obstetrics and 
      Gynecology, University of Texas Health Science Center San Antonio, Mail Code 
      7836, 7703 Floyd Curl Drive, San Antonio, Texas 78229-3900, USA.
FAU - Jansson, Nina
AU  - Jansson N
FAU - Kanai, Yoshikatsu
AU  - Kanai Y
FAU - Prasad, Puttur D
AU  - Prasad PD
FAU - Powell, Theresa L
AU  - Powell TL
FAU - Jansson, Thomas
AU  - Jansson T
LA  - eng
GR  - R01 DK089989/DK/NIDDK NIH HHS/United States
PT  - Journal Article
DEP - 20110201
PL  - United States
TA  - Endocrinology
JT  - Endocrinology
JID - 0375040
RN  - 0 (Amino Acid Transport Systems)
RN  - 0 (Carrier Proteins)
RN  - 0 (Dietary Proteins)
RN  - 0 (Eif4ebp1 protein, rat)
RN  - 0 (Insulin)
RN  - 0 (Intracellular Signaling Peptides and Proteins)
RN  - 0 (Phosphoproteins)
RN  - 0 (STAT3 Transcription Factor)
RN  - 0 (Stat3 protein, rat)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
RN  - EC 2.7.11.1 (Ribosomal Protein S6 Kinases)
RN  - EC 2.7.11.1 (Rps6kb1 protein, rat)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
SB  - IM
MH  - Amino Acid Transport Systems/metabolism
MH  - Animals
MH  - Carrier Proteins/genetics/metabolism
MH  - Diet
MH  - Dietary Proteins/*pharmacology
MH  - Female
MH  - Fetal Weight
MH  - Gene Expression Regulation/*physiology
MH  - Insulin/genetics/*metabolism
MH  - Intracellular Signaling Peptides and Proteins
MH  - Maternal Nutritional Physiological Phenomena
MH  - Phosphoproteins/genetics/metabolism
MH  - Phosphorylation
MH  - Placenta/*metabolism
MH  - Placentation
MH  - Pregnancy
MH  - Proto-Oncogene Proteins c-akt/genetics/metabolism
MH  - Rats
MH  - Ribosomal Protein S6 Kinases/genetics/metabolism
MH  - STAT3 Transcription Factor/genetics/*metabolism
MH  - Signal Transduction
MH  - TOR Serine-Threonine Kinases/genetics/*metabolism
MH  - Weight Gain
PMC - PMC3858644
EDAT- 2011/02/03 06:00
MHDA- 2011/04/28 06:00
PMCR- 2011/02/01
CRDT- 2011/02/03 06:00
PHST- 2011/02/03 06:00 [entrez]
PHST- 2011/02/03 06:00 [pubmed]
PHST- 2011/04/28 06:00 [medline]
PHST- 2011/02/01 00:00 [pmc-release]
AID - en.2010-1153 [pii]
AID - EN-10-1153 [pii]
AID - 10.1210/en.2010-1153 [doi]
PST - ppublish
SO  - Endocrinology. 2011 Mar;152(3):1119-29. doi: 10.1210/en.2010-1153. Epub 2011 Feb 
      1.