Hair and skin sterols in normal mice and those with deficient dehydrosterol reductase (DHCR7), the enzyme associated with Smith-Lemli-Opitz syndrome
详细信息 查看全文
- 作者：Montserrat Serra ; Xavier Matabosch ; Lee Ying ; Gordon Watson ; Cedric Shackleton
- 关键词：Smith-Lemli-Opitz syndrome (SLOS) ; Hair sterols ; Sterol GC/MS ; DHCR7 deficiency ; Cholesterol biosynthesis
- 刊名：The Journal of Steroid Biochemistry and Molecular Biology
- 出版年：2010
- 出版时间：November 2010
- 年：2010
- 卷：122
- 期：5
- 页码：318-325
- 全文大小：932 K
文摘
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 Δ7 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.