The ultimate objective of this study is to determine the cause of acne and to discover means for improved treatment or prevention of the disease. Acne is known to be associated with high rates of lipid secretion by the sebaceous glands in the skin, but it is not known why this results in inflammatory eruptions. Nevertheless, it has been shown that any treatment which reduces sebum production can alleviate the condition. To discover more effective and more widely applicable means for treating acne, we propose further studies on the physiology of sebaceous secretion, the biochemical pathways by which sebum is produced, the relation between sebum composition and acne, the reduction of sebum excretion by drugs, especially orally-administered synthetic derivatives of vitamin A, and the possibility of treating or preventing acne by dietary means. Absolute rates of sebum excretion will be measureed by long-term absorption of sebum from the skin surface and quantification by thin layer chromatography. The method will ber verified by measurements based on the sebum content of skin biopsies. Absolute rates of sebum production will then be correlated with sebum composition, the hormonal changes which occur during human development, and the onset and natural resolution of acne. To understand natural variations in sebum production and composition, studies will be made of the major pathways of sebum biosynthesis, including identification of the substrates from which sebum is formed, the role of phospholipids as intermediates in sebum synthesis, and reasons for variation in the content of exogenous lipids, including linoleic acid, low levels of which is sebum are assoicated with acne. Studies will be made of the linoleic acid content of sebum and the relation of this to sebum production rates and to the composition of the polar structural lipids of follicular epithelium, where abnormalities in keratinization lead to comedo formation and initiation of acne. The alleviation of acne by increased blood levels of linoleate will be attempted. Oral administration of 13-cis-retinoic acid for several months results in long-term alleviation of acne. The most appropriate dosage and regimen for this treatment will be studied, as well as the effects on absolute rates of sebum production and on sebum composition so that the mechanism of action of the drug on acne can be determined.
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