PMID- 22903823
OWN - NLM
STAT- MEDLINE
DCOM- 20130529
LR  - 20211021
IS  - 1096-0929 (Electronic)
IS  - 1096-6080 (Print)
IS  - 1096-0929 (Linking)
VI  - 130
IP  - 2
DP  - 2012 Dec
TI  - Repression of hepatobiliary transporters and differential regulation of classic 
      and alternative bile acid pathways in mice during pregnancy.
PG  - 257-68
LID - 10.1093/toxsci/kfs248 [doi]
AB  - During pregnancy, proper hepatobiliary transport and bile acid synthesis protect 
      the liver from cholestatic injury and regulate the maternal and fetal exposure to 
      bile acids, drugs, and environmental chemicals. The objective of this study was 
      to determine the temporal messenger RNA (mRNA) and protein profiles of uptake and 
      efflux transporters as well as bile acid synthetic and conjugating enzymes in 
      livers from virgin and pregnant mice on gestational days (GD) 7, 11, 14, and 17 
      and postnatal days (PND) 1, 15, and 30. Compared with virgins, the mRNAs of most 
      transporters were reduced approximately 50% in pregnant dams between GD11 and 17. 
      Western blot and immunofluorescence staining confirmed the downregulation of 
      Mrp3, 6, Bsep, and Ntcp proteins. One day after parturition, the mRNAs of many 
      uptake and efflux hepatobiliary transporters remained low in pregnant mice. By 
      PND30, the mRNAs of all transporters returned to virgin levels. mRNAs of the bile 
      acid synthetic enzymes in the classic pathway, Cyp7a1 and 8b1, increased in 
      pregnant mice, whereas mRNA and protein expression of enzymes in the alternative 
      pathway of bile acid synthesis (Cyp27a1 and 39a1) and conjugating enzymes (Bal 
      and Baat) decreased. Profiles of transporter and bile acid metabolism genes 
      likely result from coordinated downregulation of transcription factor mRNA (CAR, 
      LXR, PXR, PPARalpha, FXR) in pregnant mice on GD14 and 17. In conclusion, pregnancy 
      caused a global downregulation of most hepatic transporters, which began as early 
      as GD7 for some genes and was maximal by GD14 and 17, and was inversely related 
      to increasing concentrations of circulating 17beta-estradiol and progesterone as 
      pregnancy progressed.
FAU - Aleksunes, Lauren M
AU  - Aleksunes LM
AD  - Department of Pharmacology, Toxicology, and Therapeutics, University of Kansas 
      Medical Center, Kansas City, Kansas 66160, USA.
FAU - Yeager, Ronnie L
AU  - Yeager RL
FAU - Wen, Xia
AU  - Wen X
FAU - Cui, Julia Yue
AU  - Cui JY
FAU - Klaassen, Curtis D
AU  - Klaassen CD
LA  - eng
GR  - RR021940/RR/NCRR NIH HHS/United States
GR  - ES020522/ES/NIEHS NIH HHS/United States
GR  - R01 ES019487/ES/NIEHS NIH HHS/United States
GR  - DK081461/DK/NIDDK NIH HHS/United States
GR  - ES007079/ES/NIEHS NIH HHS/United States
GR  - ES009649/ES/NIEHS NIH HHS/United States
GR  - DK080774/DK/NIDDK NIH HHS/United States
GR  - P30ES005022/ES/NIEHS NIH HHS/United States
GR  - R01 ES020522/ES/NIEHS NIH HHS/United States
GR  - R00 DK080774/DK/NIDDK NIH HHS/United States
GR  - ES019487/ES/NIEHS NIH HHS/United States
GR  - P30 ES005022/ES/NIEHS NIH HHS/United States
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20120817
PL  - United States
TA  - Toxicol Sci
JT  - Toxicological sciences : an official journal of the Society of Toxicology
JID - 9805461
RN  - 0 (Bile Acids and Salts)
RN  - 0 (Membrane Transport Proteins)
RN  - 0 (RNA, Messenger)
RN  - 0 (Transcription Factors)
RN  - 4G7DS2Q64Y (Progesterone)
RN  - 4TI98Z838E (Estradiol)
SB  - IM
MH  - Animals
MH  - Bile Acids and Salts/blood/*metabolism
MH  - Biological Transport
MH  - Blotting, Western
MH  - Body Weight
MH  - Down-Regulation
MH  - Estradiol/blood
MH  - Female
MH  - Fluorescent Antibody Technique
MH  - Gene Expression Regulation, Enzymologic
MH  - Gestational Age
MH  - Lactation/genetics/metabolism
MH  - Liver/*metabolism
MH  - Membrane Transport Proteins/genetics/*metabolism
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Organ Size
MH  - Parturition/genetics/metabolism
MH  - Pregnancy
MH  - Progesterone/blood
MH  - RNA, Messenger/metabolism
MH  - Real-Time Polymerase Chain Reaction
MH  - Transcription Factors/genetics/metabolism
MH  - Transcription, Genetic
PMC - PMC3498745
EDAT- 2012/08/21 06:00
MHDA- 2013/05/31 06:00
PMCR- 2013/12/01
CRDT- 2012/08/21 06:00
PHST- 2012/08/21 06:00 [entrez]
PHST- 2012/08/21 06:00 [pubmed]
PHST- 2013/05/31 06:00 [medline]
PHST- 2013/12/01 00:00 [pmc-release]
AID - kfs248 [pii]
AID - 10.1093/toxsci/kfs248 [doi]
PST - ppublish
SO  - Toxicol Sci. 2012 Dec;130(2):257-68. doi: 10.1093/toxsci/kfs248. Epub 2012 Aug 
      17.