Daily fluctuation of hepatic P450 monooxygenase activities in male rats is controlled by the suprachiasmatic nucleus but remains unaffected by adrenal hormones.
Hepatic P450 monooxygenase activities, which strongly influence the efficacy and/or toxicity of drugs, are known to fluctuate daily. We also know that the P450 activities assessed by measurement of 7-alkoxycoumarin O-dealkylase (ACD) activities fluctuate daily, with apparently high values during the dark period in male rats. However, there is little knowledge about the factors that regulate daily fluctuation of P450 monooxygenase activities. In the present study using rats, we induced lesions in the suprachiasmatic nucleus (SCN) of the brain, the known site of the body's internal clock, and examined the effects on the daily fluctuation of the ACD activities to clarify the relationship between the SCN and the daily fluctuation of P450 monooxygenase activities. In addition, adrenalectomy was performed to re-evaluate the influence of adrenal hormones on the P450 activities. Our results indicated that daily fluctuations of the hepatic ACD activities were completely eliminated in the SCN-lesioned rats. However, the ACD activities in the adrenalectomized rats showed apparent daily fluctuations with high values during the dark period and low values during the light period. Therefore, this study demonstrated that the daily fluctuation of the hepatic P450 monooxygenase activities in male rats is controlled by the SCN but remains unaffected by the adrenal hormones.
Furukawa
T
T
Laboratory Animal Science and Toxicology Laboratories, Sankyo Co., Ltd., 717 Horikoshi, Fukuroi, Shizuoka 437-0065, Japan. tfuruk@fuku.sankyo.co.jp
Manabe
S
S
Watanabe
T
T
Sehata
S
S
Sharyo
S
S
Okada
T
T
Mori
Y
Y
D015660:7-Alkoxycoumarin O-Dealkylase / Q000378:metabolism; D000311:Adrenal Glands / Q000502:physiology*; D000315:Adrenalectomy; D000818:Animals; D002940:Circadian Rhythm / Q000502:physiology*; D003345:Corticosterone / Q000097:blood*; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D008099:Liver / Q000201:enzymology*; D008297:Male; D010090:Oxidoreductases, O-Demethylating / Q000378:metabolism; D051381:Rats; D011916:Rats, Inbred F344; D013493:Suprachiasmatic Nucleus / Q000293:injuries / Q000502:physiology*
D003577:Cytochrome P-450 Enzyme System; C047335:7-methoxycoumarin-O-demethylase; D010090:Oxidoreductases, O-Demethylating; D015660:7-Alkoxycoumarin O-Dealkylase; D003345:Corticosterone