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: Montserrat Serra, Xavier Matabosch, Lee Ying, Gordon Watson, Cedric Shackleton
• Journal: The Journal of steroid biochemistry and molecular biology (J Steroid Biochem Mol Biol) Vol. 122 Issue 5 Pg. 318-25 (Nov 2010) ISSN: 1879-1220 [Electronic] England
• PMID: 20804844 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2010 Elsevier Ltd. All rights reserved.

Chemical References

• Dehydrocholesterols
• Sterols
• Lanosterol
• Desmosterol
• cholesta-7,24-dien-3-ol
• lathosterol
• Cholesterol
• 7-dehydrocholesterol
• Oxidoreductases Acting on CH-CH Group Donors
• 7-dehydrocholesterol reductase

Topics

• Animals
• Cholesterol (metabolism)
• Dehydrocholesterols (metabolism)
• Desmosterol (metabolism)
• Disease Models, Animal
• Gas Chromatography-Mass Spectrometry
• Hair (chemistry)
• Lanosterol (metabolism)
• Mice
• Mutation
• Oxidoreductases Acting on CH-CH Group Donors (deficiency)
• Skin (chemistry)
• Smith-Lemli-Opitz Syndrome (genetics)
• Sterols (metabolism)