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  • Title: Effects of ethinyl estradiol and phenobarbital on bile acid synthesis and biliary bile acid and cholesterol excretion.
    Author: Davis RA, Kern F.
    Journal: Gastroenterology; 1976 Jun; 70(6):1130-5. PubMed ID: 1269874.
    Abstract:
    Bile acid synthesis calculated from respiratory (14)CO2 derived from the catabolism of [26 or 27-(14)C]cholesterol to bile acids in rats with intact enterohepatic circulations decreased 50% after 5 days of ethinyl estradiol treatment (5 mg per kg per day). Maximal derepressed bile acid synthesis, measured as biliary bile acid excretion after bile acid pool depletion, was also reduced 50% by ethinyl estradiol treatment. Because ethinyl estradiol did not alter biliary cholesterol excretion, bile contained less bile acid relative to cholesterol. Hepatic bile acid concentration was not increased by ethinyl estradiol treatment. Because the inhibitory effect of ethinyl estradiol on bile acid synthesis required 5 days of treatment it is concluded that bile acid synthesis probably was not reduced by negative feedback repression of 7alpha-hydroxylase, the rate-limiting enzyme in bile acid synthesis, which has a half-life of 2 to 3 hr. During the first 14 hr after bile duct cannulation, before bile acid pool depletion, ethinyl estradiol-treated rats excreted less than one-half as much bile acid and the same amount of cholesterol as controls. The bile acid to cholesterol ratio was therefore decreased. Rats treated simultaneously with phenobarbital and ethinyl estradiol excreted significantly more bile acid than rats treated with ethinyl estradiol alone, but biliary cholesterol excretion was not increased. The proportion of biliary bile acid relative to cholesterol was thereby restored to the control value. In contrast, after 14 hr of bile drainage and depletion of the bile acid pool, rats treated with ethinyl estradiol and those treated with phenobarbital-ethinyl estradiol excreted the same amount of bile acid. Thus, when phenobarbital is administered with ethinyl estradiol, it increases the bile acid pool size and biliary bile acid excretion, but it does not increase bile acid synthesis. The increase in pool size and biliary bile acid excretion might be due to the phenobarbital-induced increase in ileal absorption of bile acids. The effects of ethinyl estradiol and phenobarbital on bile acid synt hesis and biliary bile acid and cholesterol excretion were studied. Bile acid synthesis calculated from respiratory carbon-14-carbon dioxide derived from the catabolism of carbon-14-cholesterol to bile acids in rats with intact enterohepatic circulations decreased 50% after 5 days of ethinyl estradiol treatment (5 mg/kg/day). Maximal derepressed bile acid synthesis was also reduced 50% by ethinyl estradiol treatment. Since ethinyl estradiol did not alter biliary cholesterol excretion, bile contained less bile acid relative to cholesterol. Hepatic bile acid concentration was not increased by ethinyl estradiol treatment. It is concluded that bile acid synthesis probably was not reduced by negative feedback repression of 7 alpha-hydroxylase. During the 1st 14 hours after bile duct cannulation, before bile acid pool depletion, ethinyl-estradiol-treated rats excreted less than 1/2 as much bile acid and the same amount of cholesterol as controls. Rats treated simultaneously with phenobarbital and ethinyl estradiol excreted significantly (p less than .05) more bile acid than rats treated with ethinyl estradiol alone, but biliary cholesterol excretion was not increased. The proportion of biliary bile acid relative to cholesterol excretion was restored to control values. After 14 hours of bile drainage and depletion of the bile acid pool, rats treated with ethinyl estradiol and with the combination excreted the same amount of bile acid. Therefore, when phenobarbital is administered with ethinyl estradiol, it increases the bile acid pool size and biliary bile acid excretion but not bile acid synthesis. The phenobarbital-induced increase in ileal absorption of bile acids might be responsible for the increase in pool size and biliary bile acid excretion.
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