Kinetics and plasma concentrations of 26-hydroxycholesterol in baboons

26-Hydroxycholesterok (26OHC), a major oxysterol in human blood, is believe d to play an important role in reverse choIesterol transport, bile acid for mation, and regulation of various cellular processes. Using isotope dilutio n mass spectrometry, we measured plasma 26OHC concentrations in baboons fed either a high cholesterol/saturate fat (HC-SF) or normal chow diet. Plasma 26OHC levels in baboons were comparable to those reported for humans and w ere positively correlated with plasma cholesterol concentrations, Animals o n the HC-SF diet had significantly higher 260HC levels (0.274 +/- 0.058 mu M, mean +/- S.D.) than those on the chow diet (0.156 +/- 0.046 mu M). In se parate experiments, [H-3]26OHC was injected into four tethered baboons, and multiple blood samples drawn over a 1-h period were analyzed for [H-3]26OH C and 26OHC. Fitting the specific radioactivity data to a two-pool compartm ental model indicated a rapidly turning over plasma compartment (t(1/2) 2.9 -6.0 min) and a second compartment with slow turnover (t(1/2) 76-333 min). The calculated 26OHC production rate was 2.5 mu mol/kg body weight/day. Ass uming all 26OHC is converted to bile acids, the 26OHC production rate corre sponds to about 10% of total bile acid production in adult baboons. These r esults indicate that rapid turnover of plasma 26OHC at submicromolar concen trations could significantly contribute to bile acid synthesis. (C) 2000 El sevier Science B.V. All rights reserved.