Received for publication April 28, 2009.
Revised May 24, 2009.
Accepted for publication May 27, 2009.

Age and sex-related expression and activity of carboxylesterase 1 and 2 in mouse and human liver

Abstract

Carboxylesterase 1 (CES1) and carboxylesterase 2 (CES2) are two major hepatic hydrolases responsible for the metabolisms of numerous endogenous and exogenous compounds. In this study, age- and sex-dependent expression and activity of CES1 and CES2 were investigated utilizing both animal models and individual human liver s9 samples. The expression and activity of mouse CES1 (mCES1) and CES2 (mCES2) in the liver were markedly lower in newborns relative to adults, and increased gradually with age, approximating levels of adult animals by age 2 to 4-weeks. Similarly, the average human CES1 (hCES1) expression in the subjects < 1 year of age was significantly lower than that of pooled samples. In particular, hCES1 expression in the 13 day and 1 month-old subjects was just 20.3% and 11.1%, respectively, of the pooled sample values. Additionally, the subjects < 1 year of age exhibited a trend suggestive of low hCES2 expression, but this difference failed to reach statistical significance due to large interindividual variability. The expression and activity of mCES1 and mCES2 were not significantly altered after the animals were treated with human growth hormone, indicating growth hormone may not be associated with the low level of CES expression during early developmental stages. No significant differences of the expression and activity of mCES1 and mCES2 were observed between sexually mature male and female mice. In conclusion, the expression and activity of CES1 and CES2 are age-related, but independent of growth hormone level. Sex appears to be an unlikely factor contributing to the regulation of CES1 and CES2.

Key words: developmental pharmacology, developmental toxicology, liver microsomes, pharmacokinetics