Occurrence of isomeric dehydrocholesterols in human plasma.

Three isomeric dehydrocholesterols were found in plasma from healthy subjects and patients with abnormal produc- tion or metabolism of cholesterol. These chemically labile steroids were isolated by a mild liquid-solid extraction procedure using octadecylsilane-bonded silica as sorbent. Sterol-protein interac- tions were minimized by diluting plasma with aqueous isopropanol. The dehydrocholesterols were identified by high- performance liquid chromatography-ultraviolet spectroscopy and gas chromatography-mass spectrometry as cholesta-5,7-dien-3/3-01 (7-dehydrocholesterol), 5a-cholesta-6,8(9)-dien-3P-o1 (isode- hydrocholesterol), and tentatively as cholesta-5,8(9)-dien-3P-ol. There was a strong positive correlation between plasma levels of the two former compounds, isodehydrocholesterol levels usually being about 1.4 times higher than those of 7-dehydrocholesterol. The median concentration of 7-dehydrocholesterol in plasma from healthy subjects was 52 ng/ml. Similar concentrations were found in colectomized patients (median concentration 47 ng/ml) and patients with extrahepatic cholestasis and alcoholic liver cirrho- sis (median concentrations 79 and 67 ng/ml, respectively). Pa- tients with ileal resection or under treatment with cholestyramine had elevated levels (median concentrations 142 and 160 ng/ml, respectively) whereas patients with primary biliary cirrhosis had subnormal levels (median concentration 26 ng/ml). The results are consistent with a positive correlation between levels of the dehydrocholesterols in plasma and the rate of cholesterol synthesis. The sterols were also analyzed in human skin and bile and the results indicate that the liver may be an important source of isodehydrocholestero1.- Axelson, M. Occurrence of isomeric dehydrocholesterols in human plasma. J. Lipid Res. 1991. 32: 1441-1448. Supplementary key words 7-dehydrocholesterol vitamin D3 cholesterol biosynthesis human skin human bile 7-Dehydrocholesterol is the precursor of vitamin D3 and cholesterol in mammals. The presence of this compound in skin is well documented (l), however, studies on its oc- currence in plasma have given conflicting results. Whereas relatively high levels of the compound in plasma were reported several decades ago (2, 3), recent studies using more advanced techniques have failed to confirm this (4). In the course of studies on the biosynthesis and metabolism of vitamin D3 in humans (5), a simple method for the analysis of 7-dehydrocholesterol in plasma was de- veloped. The results show that 7-dehydrocholesterol is a