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 ex pression. With three of the substrates (alpha-naphthyl acetate and est ers 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 testost erone caused only transient increases in activity for four of the subs trates (alpha-naphthyl acetate and esters 1, 2, and 3) and no change i n activity for the other two (p-nitrophenyl acetate and ester 4). Trea tment of male and female mice with the peroxisome proliferator clofibr ate, with or without testosterone, resulted in increased hydrolysis of alpha-naphthyl acetate and p-nitrophenyl acetate, but little change f or the other substrates. Clofibrate also induced alpha-naphthyl acetat e and p-nitrophenyl acetate hydrolysis in castrated males, but clofibr ate and testosterone administered together resulted in significant inc reases of activity with all substrates, which were greater than the ad ditive effects of the two compounds administered separately. These res ults indicate that clofibrate causes significant alterations in the re gulation of esterase activity, whereas sex hormones only cause small c hanges. However, it would seem that testosterone can synergize the eff ect of clofibrate in castrated males, resulting in higher levels of ac tivity than with clofibrate alone. Finally, an overall increase in est erase activity might be due to a large increase in the activity of a f ew esterases or to a small increase in many esterases. Enzyme staining of native polyacrylamide gels reveals that the latter is true, with t he majority of esterases present in mouse liver microsomes being induc ed to a small degree by clofibrate.