| Summary: | Although the lipids of mammalian stratum corneum are known to be important for the cutaneous permeability barrier, the factors that regulate epidermal lipid biosynthesis are poorly understood. Recent studies suggest that cutaneous sterol synthesis is regulated by cutaneous barrier requirements, while the levels of circulating sterols do not play a role. Whether cutaneous barrier requirements regulate epidermal lipogenesis in general and the nature of the signal that activates the lipid biosynthetic apparatus are unknown. We determined whether alterations of the cutaneous permeability barrier, induced by treatment with a solvent (acetone), a surfactant, sodium dodecyl sulfate (SDS), or essential fatty acid deficiency (EFAD), provoked a discrete versus global stimulation of epidermal and dermal lipid biosynthesis. Acetone treatment increased epidermal, but not dermal, sterol and fatty acid biosynthesis approximately threefold over controls at 1-4 hr, which returned to normal after 12 hr. SDS treatment likewise stimulated epidermal sterol and fatty acid biosynthesis, but the increase was less dramatic than in acetone-treated animals. Since plastic occlusion blocked the expected increase in de novo lipid biosynthesis in acetone-treated animals, it is possible that water flux provides the molecular signal for de novo synthesis. Finally, EFAD mice also demonstrated enhanced epidermal sterol and fatty acid biosynthesis in comparison to normals, an effect that also was abolished when transepidermal water loss was normalized by occlusion, despite the presence of ongoing EFAD. These results demonstrate that disruption of the cutaneous permeability barrier stimulates a parallel, global boost in both sterol and fatty acid biosynthesis that is limited to the epidermis. Since such stimulation is reversed by restoration of barrier function, transcutaneous water gradients may regulate epidermal lipogenesis.
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