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PPARalpha activators down-regulate CYP2C7, a retinoic acid and testosterone hydroxylase
Li-Qun Fan1, Holly Brown-Borg, Sherri Brown
1CIIT Centers for Health Research, Six Davis Drive, PO Box 12137, Research Triangle Park, NC 27709-2137, USA.
Toxicology
|September 15, 2004
Summary
Peroxisome proliferators (PP) significantly decrease CYP2C7 mRNA and protein levels in rat livers. This suggests PPs may impact retinoic acid metabolism alongside steroid metabolism.
Area of Science:
- Toxicology
- Biochemistry
- Molecular Biology
Background:
- Peroxisome proliferators (PPs) are diverse chemicals impacting liver function via PPARalpha.
- PP exposure down-regulates specific CYP2C family members involved in hormone metabolism.
Purpose of the Study:
- To investigate the effect of PP exposure on CYP2C7, a retinoic acid and testosterone hydroxylase.
- To determine if PP exposure alters CYP2C7 gene and protein expression.
Main Methods:
- Rats were treated with WY-14,643 (WY) or gemfibrozil (GEM) for 13 weeks.
- CYP2C7 mRNA and protein levels were analyzed in liver tissues.
- Time- and dose-dependent effects of PPs on CYP2C7 were examined.
Main Results:
- WY and GEM significantly down-regulated CYP2C7 gene expression.
- WY, GEM, and di-n-butyl phthalate (DBP) decreased CYP2C7 protein levels in both sexes.
- CYP2C7 was highly sensitive to PP exposure, with effects seen at low doses and short treatment times.
Conclusions:
- PP exposure alters both CYP2C7 mRNA and protein levels.
- PPs may affect retinoic acid metabolism in addition to known impacts on steroid metabolism.