12 May


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 investi- gation  of the free fatty acids  derived from  human sebum was  conducted by Weit- kamp 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lauric acid (C12:0) and sapienic acid (C16:1D6) are the most potent antimicrobials (8; Drake  DR and  Wertz PW, unpublished observations).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  multi- methyl 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  approxi- mately   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).


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  ana- lyzed  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.


More  recently, Sebutape (Cuderm  Corporation, Dallas,  Texas,  U.S.A.)  has  been introduced for assessment of pore patterns and sebum secretion (22,23). This adsor- bant  polymeric tape  is white  but  turns transparent at the  points where sebum is adsorbed. This tape is used  after clearing  sebum from the surface,  but not depletion of the follicular  reservoir, although there  is no fundamental reason why  this could not be done. Typically,  the Sebutape is removed from the forehead after three hours, although it has been suggested that one hour would be adequate (24), and placed on a black background. The pore  pattern then  appears as black dots  on a white  back- ground, and the total black area determined by image analysis is proportional to the amount of sebum secreted (25). One can qualitatively assign  the pore pattern to one of five categories, referring to images  provided by the manufacturer: prepubertal, pubertal, acne,  mature, or senescent (26). It is also  possible to extract  lipids  from the Sebutape and  to analyze them  by thin-layer chromatography (23).

Instrumental Methods

In 1970, Schaefer  and  Kuhn-Bussius (27) demonstrated that  sebum secretion could be measured by collecting  it on a frosted glass  plate  and  measuring the transpar- ency.  As sebum is adsorbed on the  rough surface,  it spreads and  fills the  micro- scopic  pockets within the  glass.  This  smooths the  surface  and  will  result  in less light scattering when the plate  is illuminated with a beam of light. The relationship between the amount of adsorbed lipid  and  light transmission was quantitated and shown to be nonlinear. Subsequently, several  instruments based  on this  principle have  become  commercially available. The first of this is the Lipometre introduced by L’Oreal  (Aulnay’s Bois, France).  More  recently, the  Sebumeter has  been  intro- duced by Courage & Khazaka (Koln, Germany). These instruments allow measure- ments  of the  amount of sebum on  the  skin  surface  or  the  sebum secretion rate, which  can be made easily within a few minutes. However, calibration can be diffi- cult,  and  unless  the  sebaceous reservoir has  been  depleted, this  will  be the  least accurate means for measuring sebum secretion rates.

Proposed Hybrid Method

The biggest  obstacle  to accurate measurement of sebum secretion rates  is the need to deplete the sebaceous follicles. This can be overcome by 12 to 14 hours of adsorp- tion  onto  bentonite prior   to  measurement. Once  the  reservoir is  depleted, the

Sebutape method is appealing for the  actual  sebum secretion measurement. The collection  time could  be shortened to one hour,  and  a digitized image  of the Sebu- tape on its black backing  should be captured immediately. Subsequently, this image can be analyzed to estimate the sebum secretion rate  from  the total  black  area.  In addition, information on  the  number, the  pattern and  the  activity  of individual glands can be obtained. The Sebutape can be removed from  the  backing  and  the lipids  can be extracted and examined by thin-layer chromatography in conjunction with  photodensitometry. In this way, one could  obtain  two measures of the sebum secretion rate,  the  overall   lipid  class  composition and  information on  the  pore density and  variation in the activity  of individual glands.


At the time  of birth,  sebaceous glands are large  and  active, probably as a result  of androgenic stimulation in  utero   (28).  Shortly  after  birth,  the  sebaceous glands undergo atrophy and  remain relatively small  until  the  onset  of puberty. The rate of sebum secretion in prepubertal children is generally low, but there  is a measur- able  increase in sebum secretion beginning at about  an age of seven  (29). This is thought to reflect increasing secretion of dehydroepiandrosterone and  its sulfated form   from   the  adrenal  glands.  At  the  onset   of  puberty  in  males,   the  testes produce increased levels of testosterone. In the skin, this is metabolized to dihydro- testosterone, which  binds  to a cytoplasmic receptor protein. This  complex trans- locates  to  the  cell  nucleus and  modulates gene  expression (30). In  females,  the ovaries  do  produce testosterone, androstenedione, and  dehydroepiandrosterone; however, adrenal hormones are  the  major  circulating androgens in women (31). In  general, sebum secretion rates  reach  a maximum in  the  mid-teen years  and slowly  decline  thereafter as circulating androgen levels decline.

Hormonal control  of sebaceous gland activity  (Thiboutot) and  the etiology  of acne (Strauss)  are discussed at length  in later  chapters of this book.


As  noted   earlier,   sebaceous glands  are  active  in  utero   under the  influence  of maternal  hormones, and  sebaceous lipids   are  major  components of  the  vernix caseosa   (13).  Vernix   caseosa   also  contains  exfoliated  corneocytes. In  the  later stages  of development, lung  surfactant is produced and  can  be  detected in  the amniotic fluid.  This surfactant at least partially dislodges vernix  caseosa,  and  this material is ingested (32). Whether this has significance beyond possible provision of nutrients is unknown.

The mean  rate of sebaceous wax ester secretion in six-year  old boys and  girls was  5 mg/10 cm2/3 hr.  This  increased to  about  25 mg/10 cm2/3 hr  in  seven-year olds and 50 mg/10 cm2/3 hr in eight-year olds (29). There is a major, age-dependent increase in the mean  sebum secretion rate for both genders from ages 10 to 15 (33). After age 10, the mean  sebum secretion rate at any given age was always greater for males.  At age 15, the mean  wax ester secretion rates  were  0.75 mg/10 cm2/3 hr for boys  and  0.55 mg/10 cm2/3 hr  for  girls  (31,33). Sebum  secretion rates  appear to decline   exponentially thereafter,  reaching rates  approximately half  of  secretion rates  of  15-year  olds  at  about   age  50 (33). In  individuals older  than   about   65 years,  sebum secretion rates  are in the same  range  as prepubertal children.

FIGURE 1    Relative   proportions  of  ester-linked  fatty  acids   from  acylceramide  of  comedones compared with acylceramide from the  skin surface of normal  control  subjects. Abbreviation:  SC, stratum corneum. Source: From Ref. 37.

It has  long  been  established that  elevated rates  of sebum secretion are associated with  acne,  and  treatments that  lower   sebaceous gland  activity   are  therapeutic (34).  It  should be  noted   that   with   the  bentonite method  for  measurement  of sebum secretion, the  mean   sebum secretion rates  for  nonacne control   subjects, mild-to-moderate acne,  and  severe  acne  are  significantly different  with  higher secretion rates, occurring with more severe disease (35). The role of sebum in come- dogenesis and  initiation of acne and  the available therapies are discussed in later chapters of this  book.  In general, any  treatment that  significantly reduces sebum secretion is therapeutic for acne.


It has been demonstrated that sebaceous lipids  can increase the permeability of the skin (36). This was first demonstrated after application of human sebum to neonatal rat  skin  in vivo.  The  follicles  have  not  penetrated to the  surface  of the  neonatal rodent skin,  so there  is no endogenous sebum. It was  found that  the  application of human sebum to this skin surface  resulted in a two-fold increase in permeability. In addition, in accord  with  the localized essential fatty acid hypothesis, it has been shown that in comedones, sebaceous fatty acids can replace  linoleate in the acylcer- amide (37). This is illustrated in Figure  1. More  recently, it has been  reported that barrier function is impaired in acne patients compared to normal controls (38).

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