Proteins from the cytochrome P-450 CYP4A gene family metabolise hormones such as prostaglandins and other fatty acids, and are induced by peroxisome proliferators such as the hypolipidaemic drugs clofibrate and ciprofibrate. In order to better understand the function and regulation of these enzymes we have cloned a murine cDNA, Cyp4a-10, whose deduced amino acid sequence shares 92% sequence identity with rat CYP4A1. The developmental and hormonal regulation of this protein and other members of the murine Cyp4a gene family were then studied using a polyclonal antibody to rat CYP4A1. The expression of Cyp4a proteins in liver and kidney develop gradually from birth and are sexually differentiated in mature animals; growth hormone appears to be involved in regulating expression of hepatic Cyp4a proteins. The administration of phenobarbital and dexamethasone affected the expression of Cyp4a proteins in the liver, but not in the kidney, where testosterone was the key regulatory factor, demonstrating interesting tissue-specific effects in the regulation of these enzymes.
- Growth hormone
- Cytochrome P-450 regulation