Effects of bile acid administration on bile acid synthesis and its circadian rhythm in man.
In man bile acid synthesis has a distinct circadian rhythm but the relationship of this rhythm to feedback inhibition by bile acid is unknown. We measured bile acid synthesis as release of 14CO2 from [26-14C]cholesterol every 2 hr in three normal volunteers during five separate 24-hr periods. Data were fitted by computer to a cosine curve to estimate amplitude and acrophase of the circadian rhythm. In an additional six volunteers, we measured synthesis every 2 hr from 8:00 a.m. to 4:00 p.m. only. During the control period, amplitude (expressed as percentage of mean synthesis) averaged 52% and acrophase averaged 6:49 a.m. During administration of ursodeoxycholic acid (15 mg per kg per day), synthesis averaged 126% of baseline (p less than 0.1), amplitude averaged 43% and acrophase averaged 6:20 a.m. During administration of chenodeoxycholic acid (15 mg per kg per day), synthesis averaged 43% of baseline (p less than 0.001), amplitude averaged 53% and acrophase averaged 9:04 a.m. Addition of prednisone to this regimen of chenodeoxycholic acid to eliminate release of 14CO2 from corticosteroid hormone synthesis resulted in a mean amplitude of 62% and a mean acrophase of 6:50 a.m., values very similar to those in the baseline period. Administration of prednisone alone also did not significantly alter the baseline amplitude (40%) or acrophase (6:28 a.m.). We conclude that neither chenodeoxycholic acid nor ursodeoxycholic acid significantly alters the circadian rhythm of bile acid synthesis in man.(ABSTRACT TRUNCATED AT 250 WORDS)
D000328:Adult; D000368:Aged; D001647:Bile Acids and Salts / Q000096:biosynthesis / Q000494:pharmacology*; D001944:Breath Tests / Q000379:methods; D002245:Carbon Dioxide / Q000032:analysis; D002250:Carbon Radioisotopes; D002635:Chenodeoxycholic Acid / Q000494:pharmacology; D002784:Cholesterol / Q000378:metabolism; D002940:Circadian Rhythm / Q000187:drug effects*; D005260:Female; D006801:Humans; D008297:Male; D008433:Mathematics; D008875:Middle Aged; D011241:Prednisone / Q000494:pharmacology; D011422:Propionates / Q000494:pharmacology; D012016:Reference Values; D013997:Time Factors; D014580:Ursodeoxycholic Acid / Q000494:pharmacology
D001647:Bile Acids and Salts; D002250:Carbon Radioisotopes; D011422:Propionates; D002635:Chenodeoxycholic Acid; D002245:Carbon Dioxide; D014580:Ursodeoxycholic Acid; D002784:Cholesterol; D011241:Prednisone