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J Biol Chem, Vol. 273, Issue 24, 14805-14812, June 12, 1998
From the Sterol 27-hydroxylase is important for the
degradation of the steroid side chain in conversion of cholesterol into
bile acids and has been ascribed a regulatory role in cholesterol
homeostasis. Its deficiency causes the autosomal recessive disease
cerebrotendinous xanthomatosis (CTX), characterized by progressive
dementia, xanthomatosis, and accelerated atherosclerosis.
Mice with a disrupted cyp27
(cyp27 It is evident that sterol 27-hydroxylase is more important for bile
acid synthesis in mice than in humans. The results do not support the
contention that 27-hydroxylated steroids are critical for
maintenance of cholesterol homeostasis or levels of vitamin D
metabolites in the circulation.
Markedly Reduced Bile Acid Synthesis but Maintained Levels of
Cholesterol and Vitamin D Metabolites in Mice with Disrupted Sterol
27-Hydroxylase Gene
,
,,, and Department of Molecular Virology, Department
of Pathology and Laboratory Medicine, University of North Carolina,
Chapel Hill, North Carolina 37599-7525, the ** Department of
Nephrology, Hypertension and Genetics, Max-Delbrück-Center,
13122 Berlin, Germany, and the Department
of Medical Laboratory Sciences and Technology, Division of Clinical
Chemistry, Karolinska Institute, Huddinge University Hospital,
SE-141 86 Huddinge, Sweden
/) had normal plasma levels of
cholesterol, retinol, tocopherol, and 1,25-dihydroxyvitamin D. Excretion of fecal bile acids was decreased (<20% of normal), and
formation of bile acids from tritium-labeled 7
-hydroxycholesterol was less than 15% of normal. Compensatory up-regulation of hepatic cholesterol 7-hydroxylase and hydroxymethylglutaryl-CoA reductase (9- and 2-3-fold increases in mRNA levels, respectively) was
found. No CTX-related pathological abnormalities were observed. In CTX, there is an increased formation of 25-hydroxylated bile alcohols and
cholestanol. In bile and feces of the
cyp27/ mice only traces of bile alcohols
were found, and there was no cholestanol accumulation.
Copyright © 1998 by The American Society for Biochemistry and Molecular Biology, Inc.
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