27-Hydroxycholesterol: Production rates in normal human subjects

We attempted to quantitate production of bile acid via the 27- hydroxylation pathway in six human subjects. After bolus intravenous injection of known amounts of [24-¹⁴C]cholic acid and [24- ¹⁴C]chenodeoxycholic acid, each subject underwent a constant intravenous infusion of a mixture of [22,23-³H]-27-hydroxycholesterol and [²H]-27- hydroxycholesterol for 6-10 h. Production rate of 27-hydroxycholesterol was calculated from the infusion rate of [²H]-27-hydroxycholesterol and the serum ratio of deuterated/protium 27-hydroxycholesterol, which reached a plateau level by 4 h of infusion. Conversion of 27-hydroxycholesterol to cholic and chenodeoxycholic acids was determined from the ³H/¹⁴C ratio of these two bile acids in bile samples obtained the day after infusion. In five of the six subjects, independent measurement of bile acid synthesis by fecal acidic sterol output was available from previous studies. Endogenous production of 27-hydroxycholesterol averaged 17.6 mg/day and ranged from 5.0 to 28.2 mg/day, which amounted to 8.7% (range 3.0-17.9%) of total bile acid synthesis. On average 66% of infused 27-hydroxycholesterol was converted to bile acid, of which 72.6% was chenodeoxycholic acid. These data suggest that relatively little bile acid synthesis takes place via the 27-hydroxylation pathway in healthy humans. Nevertheless, even this amount, occurring predominantly in vascular endothelium and macrophages, could represent an important means for removal of cholesterol deposited in endothelium.