Daily fluctuation of hepatic P450 monooxygenase activities in male rats iscontrolled by the suprachiasmatic nucleus but remains unaffected by adrenal hormones

Hepatic P450 monooxygenase activities, which strongly influence the efficac y and/or toxicity of drugs, are known to fluctuate daily. We also know that the P450 activities assessed by measurement of 7-alkoxycoumarin O-dealkyla se (ACD) activities fluctuate daily, with apparently high values during the dark period in male rats. However, there is little knowledge about the fac tors that regulate daily fluctuation of P450 monooxygenase activities. In t he present study using rats, we induced lesions in the suprachiasmatic nucl eus (SCN) of the brain, the known site of the body's internal clock, and ex amined the effects on the daily fluctuation of the ACD activities to clarif y the relationship between the SCN and the daily fluctuation of P450 monoox ygenase activities. In addition, adrenalectomy was performed to re-evaluate the influence of adrenal hormones on the P450 activities. Our results indi cated that daily fluctuations of the hepatic ACD activities were completely eliminated in the SCN-lesioned rats. However, the ACD activities in the ad renalectomized rats showed apparent daily fluctuations with high values dur ing the dark period and low values during the light period. Therefore, this study demonstrated that the daily fluctuation of the hepatic P450 monooxyg enase activities in male rats is controlled by the SCN but remains unaffect ed by the adrenal hormones.