The Effects of Phenobarbital, Spironolactone and Diazepam on Hepatic 3-Hydroxy-3-methylglutaryl Coenzyme A Reductase Activity in Male and Female Rats

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The specific activity of hepatic microsomal 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMG-CoA reductase) was examined at noon and at midnight in rats of both sexes pretreated with phenobarbital, spironolactone, or diazepam. In female rats, phenobarbital pretreatment significantly increased the activity of the enzyme at midnight, but the activity at noon remained unaltered. In male rats, the activity was unchanged by phenobarbital pretreatment both at noon and at midnight, while in castrated rats, the activity was increased significantly at midnight by pretreatment with phenobarbital. Spironolactone pretreatment decreased the activity at midnight but increased the activity at noon in both sexes. In adrenalectomized male rats, the activity in rats pretreated with spironolactone was unchanged both at noon and at midnight, compared with untreated adrenalectomized rats. Diazepam pretreatment increased the activity at noon and kept it unchanged at midnight in both sexes. It is suggested that the effect of these drugs on HMG-CoA reductase should be carefully examined in view of the variability of the effect between day and night as well as the sex-dependent differences in rats.
1983-11-25