Sex difference in the daily rhythm of hepatic P450 monooxygenase activities in rats is regulated by growth hormone release

Daily fluctuations have been observed in the hepatic cytochrome P450 monoox ygenase activities of rodents. It was confirmed in our previous study that the P450 activities assessed by measurement of 7-alkoxycoumarin O-dealkylas e (ACD) showed obvious daily fluctuations in male rats with high values dur ing the dark period. However, there is still very little information about the daily fluctuation of P450 activities in female rats. In the first exper iment of the present study, the daily fluctuation of ACD activities in fema le rats was examined. The results indicated the absence of any apparent dai ly fluctuation in the hepatic ACD activities of the females, so the study c onfirmed a sex difference in the daily rhythm of the ACD activities. In the second experiment using hypophysectomized (Hpx) rats, it was investigated whether this sex difference in daily rhythm was attributable to growth horm one (GH) release, an activity which is known to affect the sex difference i n the expression of P450 isoforms. It was found that the Hpx rats, given su bcutaneous injections of GH twice during the light period to mimic a male p attern of GH secretion, showed obvious Light-dark fluctuation in ACD activi ties with high values in the dark period, and similar results were obtained in sham-operated males. Conversely, the Hpx rats given continuous infusion of GH to mimic a female pattern of GH secretion did not show the light-dar k fluctuation in ACD activities, and similar results were obtained in sham- operated females. In conclusion, there is a sex difference in the daily rhy thm of the hepatic P450 activities in rats and this difference is apparentl y influenced by the difference in the patterns of GH secretions. (C) 1999 A cademic Press.