Abstract
SUMMARY Skin of normal rats and of rats treated with triparanol were incubated with acetate-2-H3 for 2 hr, and the sterols were extracted and separated chromatographically. Treatment with triparanol resulted in grossly visible changes (scaliness, roughness, and atrophy of the skin) and in a marked alteration in the metabolism of skin sterols. There were considerable reductions in the concentrations of compounds with saturated side chains: cholesterol, methostenol, and dihydrolanosterol; and increases in the concentrations of sterols with unsaturated side chains: desmosterol, lanosterol, and sterols tentatively identified as dehydromethostenol and A7,24-cholestadienol. Isotope data showed that after incubation for 2 hr, a large proportion of the counts were in squalene in skin from both normal and triparanoltreated rats. There was a reduction in the incorporation of radioactivity into the A5-stenol fraction and an increase in the incorporation into lanosterol and A7-sterols, in skin from triparanol-treated rats. Triparanol inhibits the enzyme responsible for reduction of the 24,25double bond in the sterols of rat skin. The mechanism of sterol biosynthesis in mammalian skin is generally believed to be similar to that in the rest of the organism. The composition of the skin sterols, however, differs markedly from their compoeition in other organs. Skin contains significantly higher concentrations of various sterols that serve as normal intermediates in the biosynthesis of cholesterol. Skin, then, would appear to be an ideal site for studying the biosynthesis of cholesterol in normal animals and for observing the effects of inhibitors of biosynthesis. Previous studies on the composition of rat skin include those of Moore and Baumann (I), who identified 7-dehydrocholesterol among the “fast-acting” sterols from rat skin, and Idler and Baumann (a), who found that A7-cholestenol represents up to SOYo of the total sterol fraction. It is interesting to note that AI-cholestenol is less abundant in other mammals (3). Keiderhiser and Wells (4) reported the presence of 4amethyl-A’-cholestenol (methostenol) in rat skin and other tissues, and Stokes et al. (5) identified 24-dehydrocholesterol (desmosterol) as a normal constituent of
Highlights
Desmosterol was later identified as a major sterol in the tissues of rats treated with triparanol, indicating an inhibition of the reduction of the 24,25
Ai-cholestenol, 7-dehydrocholesterol, desmosterol, dihydrolanosterol, lanosterol, and methostenol were used for identification of the various peaks obtained by G I X and as standards for quantitative analysis
Upon Gas-liquid chromatography (GLC) of the compounds in zone 6 (A7-stenoIs),a new peak appeared, which had not been seen in the normal rat, and which we believe to be A7tZ4(or A8~24-)cholestadienfoolr reasons given below
Summary
Laboratory of Metabolism, National Heart Institute, National Institutes of Health, Bethesda 14, Maryland [Manuscriptreceived September 24,1962; accepted November 21,1962.1. SUMMARY Skin of normal rats and of rats treated with triparanol were incubated with acetate-2-H3 for 2 hr, and the sterols were extracted and separated chromatographically. Desmosterol was later identified as a major sterol in the tissues of rats treated with triparanol, indicating an inhibition of the reduction of the 24,25-. Ai-cholestenol, 7-dehydrocholesterol, desmosterol, dihydrolanosterol, lanosterol, and methostenol were used for identification of the various peaks obtained by G I X and as standards for quantitative analysis. The skins of the treated rats showed gross morphological changes from
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