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-C-14]cholic acid and [24-C-14]chenodeoxycholic acid, each su bject underwent a constant intravenous infusion of a mixture of [22,23-H-3] -27-hydroxycholesterol and [H-2]-27-hydroxycholesterol for 6-10 h. Producti on rate of 27-hydroxycholesterol was calculated from the infusion rate of [ H-2]-27-hydroxycholesterol and the serum ratio of deuterated/protium 27-hyd roxycholesterol, which reached a plateau level by 4 h of infusion. Conversi on of 27-hydroxycholesterol to cholic and chenodeoxycholic acids was determ ined from the H-3/C-14 ratio of these two bile acids in bile samples obtain ed the day after infusion. In five of the six subjects, independent measure ment of bile acid synthesis by fecal acidic sterol output was available fro m 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% (ra nge 3.0-17.9%) of total bile acid synthesis. On average 66% of infused 27-h ydroxycholesterol was converted to bile acid, of which 72.6% was chenodeoxy cholic acid. These data suggest that relatively little bile acid synthesis takes place via the 27-hydroxylation pathway in healthy humans. Nevertheles s, even this amount, occurring predominantly in vascular endothelium and ma crophages, could represent an important means for removal of cholesterol de posited in endothelium.