Sebum Secretion and Acne

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Philip W. Wertz

Dows Institute, University of Iowa, Iowa City, Iowa, U.S.A.

COMPOSITION OF HUMAN SEBUM

Sebum is synthesized in sebaceous glands, which are part of the pilosebaceous units of the skin (1). Sebaceous glands are epidermal appendages found in all regions of the skin, except the palmar and plantar surfaces; however, the greatest density of glands is found in the scalp and facial areas.

As sebocytes move from the basal layer at the periphery of the gland toward the lumen, they synthesize neutral lipids, which accumulate as lipid droplets, and eventually all of the carbon-based components of the cell are converted into lipid. The composition of sebum is species-specific. Human sebum, as it is synthesized in the gland (2), consists of squalene (15%), wax esters (25%), cholesterol esters (2%), triglycerides (57%), and cholesterol (1%). The small proportion of free cholesterol and cholesterol esters are thought to be derived from cholesterol in the basal sebo-cyte plasma membrane. Differentiating sebocytes do not express the enzymes of the cholesterol biosynthetic pathway beyond those leading to the production of squa-lene (3). This mixture of sebaceous lipids is liquid phase at skin tempertature.

As it flows out through the follicle and over the skin surface, the triglycerides undergo at least partial hydrolysis to liberate free fatty acids (4). The first investigation of the free fatty acids derived from human sebum was conducted by Weitkamp et al. in 1947 (5). Using fractional distillation, fatty acids ranging from 7 through 22 carbons in length were detected. Shorter chains may have been present, but the 7-carbon entity was the shortest that could be detected. In addition, series of D6- and D9-monoenes were identified, with the D6 series dominating. The 16- and 18-carbon species were the most abundant. Small proportions of 1,2-diglycerides and 1,3-diglycerides are also produced through lipase action (4). The esterases responsible for sebaceous triglyceride hydrolysis are bacterial (6) and probably also of epidermal origin (7).

Of the fatty acids released from sebaceous triglycerides lauric acid (C12:0) and sapienic acid (C16:1D6) are the most potent antimicrobials (8; Drake DR and Wertz PW, unpublished observations). Sapienic acid is the single most abundant fatty acid in human sebum and is not found in abundance in any other known source, whereas lauric acid is a relatively minor sebaceous fatty acid. These two fatty acids both have potent antimicrobial properties, especially against gram-positive bacteria.

Frequently, alkanes are found in lipid samples collected from the human skin surface. Carbon dating has proven this material to be derived from petroleum (9), although it is not certain if it is simply surface contamination, as opposed to an internalized contaminant that is delivered to the skin surface through the sebaceous secretions.

In addition to the sebaceous lipids synthesized in the gland, hydrophobic materials from the circulation may partition into the sebaceous glands. This includes the antioxidants vitamin E (10,11) and coenzyme Q10 (11). Sebum secretion appears to be the major route for delivery of these antioxidant vitamins to the skin surface. This may be of particular significance for defense against reactive oxygen species and protection of the linoleate containing acylceramides in the stratum corneum (12).

The major fatty acids in human sebum range in length from 12 carbons through 20 carbons, with the 16- and 18-carbon species predominating (13,14). In prepubertal children, some longer fatty chains are found (15). As noted, C16:1D6 is the most abundant fatty acid in human sebum. C18:1D8 is produced from C16:1D6 by chain extension. An unusual characteristic of human sebum is the presence of various methyl branched fatty acids (13,14). These include saturated iso- and anteisomethyl branched chains, but also various other internal and multimethyl branched chains. The methyl branching pattern of saturated fatty acids varies among individuals, but is invariant with time for a given individual (14). This indicates genetic control.

Saturated and monounsaturated fatty acids predominate in the sebaceous esters with only small proportions of dienes being present (4). Among the wax ester fatty acids, the saturated-to-monounsaturated fatty acid ratio is approximately 40 to 60; whereas in the cholesterol ester and triglyceride fractions this ratio is 65:35 and 70:30, respectively (13,16). The dienoic fatty acids include linoleic acid (C18:2 D9,12), derived from the diet, and an isomer thereof (C18:2 D5,8), which is synthesized in the gland (17). The proportion of C18:2 D9,12 relative to C18:2 D5,8 is decreased in acne. This is consistent with the suggestion that comedogenesis is initiated by a localized essential fatty acid deficiency (18).

MEASUREMENT OF SEBUM SECRETION Cigarette Paper Method

One of the most widely used methods for measurement of sebum secretion rates is the cigarette paper method of Strauss and Pochi (19). In this method, the forehead was first cleansed to remove surface lipid. A previously extracted cigarette paper was then placed against the skin of the forehead and held in place with an ace bandage. After a three-hour collection period, the cigarette paper was removed. Lipids were extracted from the paper using ethyl ether and quantitated either by weighing (19) or by quantitative thin-layer chromatographic analysis (4,20).

Bentonite Method

Subsequently, bentonite has been used to adsorb sebum on the forehead (21). After washing the forehead with soap and water and swabbing with an ethanol-soaked gauze pad, a thin layer of bentonite gel was applied to the forehead. In initial studies, two 1.8-mm diameter circular disks of Dacron mesh were pressed into the bentonite, and these were covered with additional bentonite. At three hours interval thereafter, the Dacron disks and adhering bentonite were replaced and sampling continued to 24 hours. The amount of sebum adsorbed per disk over three hours decreased steadily for about the first 12 hours, after which the rate of sebum secretion became constant. The excess sebum secreted during the initial 12 hours of collection was interpreted as a reflection of a follicular reservoir. Only after this reservoir was depleted was the sustainable sebum secretion rate measurable. This sustainable secretion rate is equal to the rate of synthesis in the glands. In later studies, bentonite was applied to the forehead, and a rectangular piece of Dacron mesh large enough to cover most of the forehead was pressed into the gel and covered with additional bentonite. After seven hours, the Dacron mesh on the forehead was replaced, and after another seven hours to deplete the reservoir, the rectangular Dacron was replaced with two circular disks of Dacron for a final three-hour collection period, reflecting the sustainable rate of sebum secretion. The lipids were extracted from the bentonite into ethyl ether and analyzed by quantitative thin-layer chromatography. In a variant on this method, the final collection period after depletion of the follicular reservoir was extended to nine hours, and the extracted sebum was quantitated gravimetrically.

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