title: Hair and skin sterols in normal mice and those with deficient dehydrosterol reductase (DHCR7), the enzyme associated with Smith-Lemli-Opitz syndrome.
abstract: Our recent studies have focused on cholesterol synthesis in mouse models for 7-dehydrosterolreductase (DHCR7) deficiency, also known as Smith-Lemli-Opitz syndrome. Investigations of such mutants have relied on tissue and blood levels of the cholesterol precursor 7-dehydrocholesterol (7DHC) and its 8-dehydro isomer. In this investigation by gas chromatography/mass spectrometry (GC/MS) we have identified and quantified cholesterol and its precursors (7DHC, desmosterol, lathosterol, lanosterol and cholest-7,24-dien-3β-ol) in mouse hair. The components were characterized and their concentrations were compared to those found in mouse skin and serum. Hair appeared unique in that desmosterol was a major sterol component, almost matching in concentration cholesterol itself. In DHCR7 deficient mice, dehydrodesmosterol (DHD) was the dominant hair Δ(7) sterol. Mutant mouse hair had much higher concentrations of 7-dehydrosterols relative to cholesterol than did serum or tissue at all ages studied. The 7DHC/C ratio in hair was typically about sevenfold the value in serum or skin and the DHD/D ratio was 100× that of the serum 7DHC/C ratio. Mutant mice compensate for their DHCR7 deficiency with maturity, and the tissue and blood 7DHC/C become close to normal. That hair retains high relative concentrations of the dehydro precursors suggests that the apparent up-regulation of Dhcr7 seen in liver is slower to develop at the site of hair cholesterol synthesis.
authors.affiliation: Children's Hospital Oakland Research Institute, Oakland, CA 94609, USA.
authors.forename: Montserrat
authors.initials: M
authors.lastname: Serra
authors.forename: Xavier
authors.initials: X
authors.lastname: Matabosch
authors.forename: Lee
authors.initials: L
authors.lastname: Ying
authors.forename: Gordon
authors.initials: G
authors.lastname: Watson
authors.forename: Cedric
authors.initials: C
authors.lastname: Shackleton
mesh_terms: D000818:Animals; D002784:Cholesterol / Q000378:metabolism; D003684:Dehydrocholesterols / Q000378:metabolism; D003897:Desmosterol / Q000378:metabolism; D004195:Disease Models, Animal; D008401:Gas Chromatography-Mass Spectrometry; D006197:Hair / Q000737:chemistry*; D007810:Lanosterol / Q000378:metabolism; D051379:Mice; D009154:Mutation; D044925:Oxidoreductases Acting on CH-CH Group Donors / Q000172:deficiency*; D012867:Skin / Q000737:chemistry*; D019082:Smith-Lemli-Opitz Syndrome / Q000235:genetics; D013261:Sterols / Q000378:metabolism*
chemical_list: D003684:Dehydrocholesterols; D013261:Sterols; D007810:Lanosterol; D003897:Desmosterol; C007040:cholesta-7,24-dien-3-ol; C001521:lathosterol; D002784:Cholesterol; C016705:7-dehydrocholesterol; D044925:Oxidoreductases Acting on CH-CH Group Donors; C019995:7-dehydrocholesterol reductase
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