PMID- 9730905
OWN - NLM
STAT- MEDLINE
DCOM- 19981005
LR  - 20190607
IS  - 0026-895X (Print)
IS  - 0026-895X (Linking)
VI  - 54
IP  - 3
DP  - 1998 Sep
TI  - Down-regulation of cytochrome P450 2C family members and positive acute-phase 
      response gene expression by peroxisome proliferator chemicals.
PG  - 463-73
AB  - In this study, we show that peroxisome proliferator chemical (PPC) exposure leads 
      to alterations in the expression of genes in rat liver regulated by the 
      sex-specific growth hormone secretory pattern and induced during inflammation. 
      Expression of the male-specific cytochrome P450 (P450) 2C11 and alpha2 urinary 
      globulin (alpha2u) genes and the female-specific P450 2C12 gene was 
      down-regulated by some PPC. Expression of P450 2C13, also under control by the 
      sex-specific growth hormone secretory pattern, was not altered by PPC treatment, 
      indicating that regulation of CYP2C family members does not involve perturbation 
      of the growth hormone secretory pattern. In contrast to the increases in 
      expression observed when inflammation was induced in male rats, two positive 
      acute-phase response genes, alpha1-acid glycoprotein and beta-fibrinogen, were 
      decreased by PPC exposure. The down-regulation of the P450 2C11 by WY-14,643 
      could be reproduced in cultured rat hepatocytes, indicating the down-regulation 
      is a direct effect. Experiments in wild-type mice and mice that lacked a 
      functional peroxisome proliferator-activated receptor-alpha gene showed that 
      down-regulation by WY of alpha1-acid glycoprotein, beta-fibrinogen, and a mouse 
      homologue of alpha2u was dependent on peroxisome proliferator-activated 
      receptor-alpha expression. Our results demonstrate that PPC exposure leads to 
      down-regulation of diverse liver-specific genes, including CYP2C family members 
      important in hormonal homeostasis and acute-phase response genes important in 
      inflammatory responses.
FAU - Corton, J C
AU  - Corton JC
AD  - Chemical Industry Institute of Toxicology, Research Triangle Park, North Carolina 
      27709, USA. corton@ciit.org
FAU - Fan, L Q
AU  - Fan LQ
FAU - Brown, S
AU  - Brown S
FAU - Anderson, S P
AU  - Anderson SP
FAU - Bocos, C
AU  - Bocos C
FAU - Cattley, R C
AU  - Cattley RC
FAU - Mode, A
AU  - Mode A
FAU - Gustafsson, J A
AU  - Gustafsson JA
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Mol Pharmacol
JT  - Molecular pharmacology
JID - 0035623
RN  - 0 (Acute-Phase Proteins)
RN  - 0 (Alpha-Globulins)
RN  - 0 (Receptors, Cytoplasmic and Nuclear)
RN  - 0 (Transcription Factors)
RN  - 0 (alpha 2u globulin)
RN  - 9035-51-2 (Cytochrome P-450 Enzyme System)
RN  - EC 1.14.- (Steroid Hydroxylases)
RN  - EC 1.14.14.1 (Aryl Hydrocarbon Hydroxylases)
RN  - EC 1.14.14.1 (Steroid 16-alpha-Hydroxylase)
SB  - IM
MH  - Acute-Phase Proteins/metabolism
MH  - Acute-Phase Reaction/*enzymology/*genetics
MH  - Alpha-Globulins/biosynthesis/genetics
MH  - Animals
MH  - *Aryl Hydrocarbon Hydroxylases
MH  - Cells, Cultured
MH  - Cytochrome P-450 Enzyme System/*biosynthesis/*genetics
MH  - Down-Regulation/drug effects
MH  - Female
MH  - Gene Expression Regulation, Enzymologic/*drug effects
MH  - Liver/drug effects/enzymology/*physiology
MH  - Male
MH  - Mice
MH  - Microbodies/*drug effects
MH  - Rats
MH  - Rats, Inbred F344
MH  - Rats, Sprague-Dawley
MH  - Receptors, Cytoplasmic and Nuclear/physiology
MH  - *Steroid 16-alpha-Hydroxylase
MH  - Steroid Hydroxylases/*biosynthesis/*genetics
MH  - Transcription Factors/physiology
EDAT- 1998/09/09 00:00
MHDA- 1998/09/09 00:01
CRDT- 1998/09/09 00:00
PHST- 1998/09/09 00:00 [pubmed]
PHST- 1998/09/09 00:01 [medline]
PHST- 1998/09/09 00:00 [entrez]
AID - 10.1124/mol.54.3.463 [doi]
PST - ppublish
SO  - Mol Pharmacol. 1998 Sep;54(3):463-73. doi: 10.1124/mol.54.3.463.