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 monooxygenase activities of rodents. It was confirmed in our previous study that the P450 activities assessed by measurement of 7-alkoxycoumarin O-dealkylase (ACD) showed obvious daily fluctuations in male rats with high values during the dark period. However, there is still very little information about the daily fluctuation of P450 activities in female rats. In the first experiment of the present study, the daily fluctuation of ACD activities in female rats was examined. The results indicated the absence of any apparent daily fluctuation in the hepatic ACD activities of the females, so the study confirmed 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 hormone (GH) release, an activity which is known to affect the sex difference in the expression of P450 isoforms. It was found that the Hpx rats, given subcutaneous injections of GH twice during the light period to mimic a male pattern of GH secretion, showed obvious light-dark fluctuation in ACD activities 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-dark fluctuation in ACD activities, and similar results were obtained in sham-operated females. In conclusion, there is a sex difference in the daily rhythm of the hepatic P450 activities in rats and this difference is apparently influenced by the difference in the patterns of GH secretions.
Furukawa
T
T
Medicinal Safety Research Laboratories, Sankyo Co., Ltd., Shizuoka, Japan. tfuruk@fuku.sankyo.co.jp
Manabe
S
S
Watanabe
T
T
Sharyo
S
S
Mori
Y
Y
D015660:7-Alkoxycoumarin O-Dealkylase / Q000378:metabolism; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D002940:Circadian Rhythm / Q000502:physiology*; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D004971:Estrus / Q000187:drug effects / Q000502:physiology; D005260:Female; D013006:Growth Hormone / Q000008:administration & dosage / Q000378:metabolism*; D007016:Hypophysectomy; D015918:Infusion Pumps, Implantable; D007279:Injections, Subcutaneous; D008297:Male; D008862:Microsomes, Liver / Q000201:enzymology*; D010090:Oxidoreductases, O-Demethylating / Q000378:metabolism; D051381:Rats; D011916:Rats, Inbred F344; D012727:Sex Characteristics
D013006:Growth Hormone; D003577:Cytochrome P-450 Enzyme System; C047335:7-methoxycoumarin-O-demethylase; D010090:Oxidoreductases, O-Demethylating; D015660:7-Alkoxycoumarin O-Dealkylase