Regulation of mouse liver microsomal esterases by clofibrate and sexual hormones

Carboxylesterase activity was measured using six different substrates in microsomal preparations from female and ovariectomized female mice in order to evaluate the effects of female sex hormones on esterase expression. With three of the substrates (α-naphthyl acetate and esters 2 and 3), esterase activity was the same in both groups; however, with the others (p-nitrophenyl acetate and esters 1 and 4), there was a small increase in activity in ovariectomized females, compared with intact females. Castration of males followed by treatment with testosterone caused only transient increases in activity for four of the substrates (α-naphthyl acetate and esters 1, 2, and 3) and no change in activity for the other two (p-nitrophenyl acetate and ester 4). Treatment of male and female mice with the peroxisome proliferator clofibrate, with or without testosterone, resulted in increased hydrolysis of α-naphthyl acetate and p-nitrophenyl acetate, but little change for the other substrates. Clofibrate also induced α-naphthyl acetate and p-nitrophenyl acetate hydrolysis in castrated males, but clofibrate and testosterone administered together resulted in significant increases of activity with all substrates, which were greater than the additive effects of the two compounds administered separately. These results indicate that clofibrate causes significant alterations in the regulation of esterase activity, whereas sex hormones only cause small changes. However, it would seem that testosterone can synergize the effect of clofibrate in castrated males, resulting in higher levels of activity than with clofibrate alone. Finally, an overall increase in esterase activity might be due to a large increase in the activity of a few esterases or to a small increase in many esterases. Enzyme staining of native polyacrylamide gels reveals that the latter is true, with the majority of esterases present in mouse liver microsomes being induced to a small degree by clofibrate.