Submitted on January 11, 2008
Accepted on February 15, 2008
Increased cytochrome P450 7
-hydroxylase expression and size of the bile acid pool in the lactating rat
Clavia Ruth Wooton-Kee1, David E. Cohen2, and Mary Vore1*
1 Toxicology, University of Kentucky, Lexington, Kentucky, United States
2 Division of Gastroenterology, Brigham and Women's Hospital, Boston, Massachusetts, United States
* To whom correspondence should be addressed. E-mail: maryv{at}uky.edu.
Maximal bile acid secretory rates and expression of bile acid transporters in liver and ileum are increased in lactation, possibly to facilitate increased enteroheptic recirculation of bile acids. We determined changes in the size and composition of the bile acid pool and key enzymes of the bile acid synthetic pathway (Cyp7a1, Cyp27a1, Cyp8b1) in lactating rats relative to female virgin controls. The bile acid pool increased 1.9 to 2.5-fold (postpartum days 10, 14, and 19-23), compared to controls. A 1.5-fold increase in cholic acids and a 14 to 20 % decrease in muricholic acids in lactation significantly increased the hydrophobicity index. In contrast, the hepatic concentration of bile acids and SHP mRNA were unchanged in lactation. A 2.8-fold increase in Cyp7a1 mRNA expression at 16 h (10 h of light) demonstrated a shift in the diurnal rhythm at day 10 postpartum; Cyp7a1 protein expression and cholesterol 7
-hydroxylase activity were significantly increased at this time and remained elevated at day 14 postpartum but decreased to control levels by day 21 postpartum. There was an overall decrease in Cyp27a1 mRNA expression and a 20% decrease in Cyp27a1 protein expression, but there was no change in Cyp8b1 mRNA or protein expression at day 10 postpartum. The increase in Cyp7a1 expression postpartum provides a mechanism for the increase in the bile acid pool.
