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Sebaceous Glands, Sebum, the Skin Barrier, Cornified Envelope and Glutamine
The oil on the surface of skin is a complex mixture of sebum, lipids (from the surface skin cells), sweat and environmental material.
Sebum is produced by sebaceous glands. These are found over most of the body, although there are few on the hands or feet and none on the palms and soles. Sebaceous glands on the mid-back, forehead and chin are larger and more numerous than elsewhere (up to 400-900 glands per square centimetre). They are also numerous in the ear canal and around the genitals.
The sebaceous gland consists of lobes connected by ducts, which are lined with cells similar to those on the skin surface.
Most sebaceous glands open out into the hair follicle. Some free sebaceous glands open directly onto the skin surface. These include Meibomian glands on the eyelids, Tysons glands on the foreskin and Fordyce spots on the upper lip or genitals.
Sebum is produced when the sebaceous gland disintegrates. The cells take about a week from formation to discharge. Sebum is a complex and variable mixture of lipids including:
- Glycerides
- Free fatty acids
- Wax esters
- Squalene
- Cholesterol esters
- Cholesterol
Triglycerides produced by sebaceous glands are broken down by bacterial enzymes (lipases) in the sebaceous duct to form free fatty acids.
Lipase Test (National Institute of Health)
Lipase is a protein (enzyme) released by the pancreas into the small intestines. It triggers the breakdown of fat into fatty acids.
What Does Sebum Normally Do?
Sebum has the following functions:
- It reduces water loss from the skin surface
- It protects the skin from infection by bacteria and fungi
- It contributes to body odour
- It is colonised by the bacteria Proprionibacterium acnes, which may have a role in immune regulation
Hormonal Control of Sebum
Sebum production is under the control of sex hormones (androgens). The most active androgens are testosterone, 5-testosterone (DHT) and 5-androstene-317diol. These hormones and others are made by the sex glands (ovary in females, testis in males) and by the adrenal gland. These glands are in turn under the influence of the pituitary gland, located in the brain.
Androgens are made more active by enzymes in the skin and sexual organs. Type 1 5- reductase acts in the skin and Type II 5- reductase acts in the sexual organs. These enzymes convert less active androgens into the active testosterone and 5-testosterone (DHT). These more active androgens stimulate sebaceous gland cells to produce more sebum.
The role of progesterone is unclear. Females produce more sebum in the week before their menstrual period when progesterone levels are higher. But progesterone is known to reduce the activity of the enzyme 5-reductase that one might expect to reduce sebum production.
Sebum Varies with Age
Sebaceous glands are already active before birth. They are regulated by the mothers hormones and those made by the fetus itself.
The composition of oils on the skin surface varies with age. Excessive sebum production is known as seborrhoea.
- The fetus produces vernix caseosa, a waxy protective layer
- For 3 to 6 months, sebum produced by a newborn baby resembles that of an adult
- Thereafter until the age of 8 it has less wax and squalene and more cholesterol
- Sebum production increases at puberty up to fivefold in men
- Adult males produce slightly more sebum than adult females
- Sebum production declines with age, particularly after menopause in females
The amount of sebum can be altered by disease:
- Pituitary, adrenal, ovarian or testicular disorders may increase or reduce it
- Prolonged starvation reduces the amount of sebum
- Parkinson's disease increases the amount of sebum
The amount can be reduced by certain systemic medications:
- Oestrogens (oral contraceptive pill)
- Antiandrogens such as cyproterone acetate and spironolactone
- Vitamin-A derivatives such as isotretinoin
The amount can be increased by other systemic medications:
- Testosterone given to prepubertal males
- Progesterones with androgenic properties such as medroxyprogesterone, levonorgestrel
- Phenothiazines
The proportion of different components may change with certain medications:
- Diane-35® / Estelle-35®,containing ethinyl (o)estradiol 35mcg and cyproterone 2mg, increases linoleate
- Isotretinoin reduces squalene, wax esters and fatty esters
Barrier Function
linkinghub.elsevier.com/retrieve/pii/S0923181106001733
Skin permeability barrier function is impaired in eczema, particularly in contact and atopic dermatitis (AD). In contact dermatitis disruption of the barrier by irritants and allergens is the primary event, followed by sensitization, inflammation, increased epidermal proliferation and changes in differentiation. Genetically impaired skin barrier function is already present in non-lesional and more pronounced in lesional skin in AD. Increased epidermal proliferation and disturbed differentiation, including changes in lipid composition, cause impaired barrier function in AD. Defective permeability barrier function enables the enhanced penetration of environmental allergens into the skin and initiates immunological reactions and inflammation. Barrier dysfunction is therefore crucially involved in the pathogenesis of AD. The atopic syndrome represents a genetically impaired skin barrier function as well as impaired nasal, bronchial, and intestinal mucous membranes leading to AD, allergic rhinitis, bronchial asthma or aggravation of AD. Common treatment strategies for eczema include the application of lipid-based creams and ointments, which aim toward the restoration of the defective permeability barrier, thus helping to normalize proliferation and differentiation.
Sun Increases Sebum Production
Stimulating Sebum Production
Hormones and Sebum Production
Sebum Protects the Skin from Infection
Reduces Water Loss from the Skin
The underactive oil gland produces inadequate oil secretions that lead to insufficient lubrication of the skin’s surface. Lack of natural sebum diminishes its ability to retain moisture, since oil in the skin acts as a natural barrier against moisture loss. Sebum acts to protect and waterproof hair and skin and keeps them from becoming dry, brittle and cracked by dehydration. It can also inhibit the growth of some microorganisms (such as some bacteria) on the skin.
Glutamine Amino Acid in Proliferation
Glutamine is a nutrient for immune cells and acts as precursor for glutathione, which circumvents oxidant stress and improves cell-mediated immunity.1
Cholesterol 3-Sulfate Interferes with Cornified Envelope Assembly by Diverting Transglutaminase 1 Activity from the Formation of Cross-links and Esters to the Hydrolysis of Glutamine 2
From Biochemistry of Skin
The skin contains all the enzymes needed for transformation of cholesterol to steroids. Moreover, the sebaceous glands express 5a-reductase (especially in face/scalp), needed for the intracellular conversion of testosterone to the more potent 5a-dihydrotestosterone. Moreover, these glands are part of the skin neuroendocrine system as they produce and release corticotrophin-releasing hormone (in response to stress). The human sebaceous gland is both glycolytic and glutaminolytic; the sugar glucose is converted to lactate, and glutamine is converted to glutamate, alanine, serine, glycine, threonine, lactate and ammonia. Recently, it has been shown that exogenous glutamine is required for sebocyte division and lipogenesis, though it can be replaced by spermidine.
Lipogenesis in Human Sebaceous Gland: Glycogen & Glycerophosphate are Substrates for the Synthesis of Sebum Lipids
Although preliminary experiments have shown that human sebaceous glands engage in glutaminolysis, and also that, in the absence of glutamine, rates of lipogenesis and DNA synthesis are reduced, glutamine demonstrated poor lipogenic capacity. This may suggest that, although glutamine may be important for sebaceous cell proliferation, in contrast to the hair follicle (Williams et al. 1993) the sebaceous gland does not utilize glutamine as an important catabolic fuel.
Keratinocytes as Depository of Ammonium-Inducible Glutamine Synthetase: Age- and Anatomy-Dependent Distribution in Human and Rat Skin
In inner organs, glutamine contributes to proliferation, detoxification and establishment of a mechanical barrier, i.e., functions essential for skin, as well. However, the age-dependent and regional peculiarities of distribution of glutamine synthetase (GS), an enzyme responsible for generation of glutamine, and factors regulating its enzymatic activity in mammalian skin remain undisclosed. .... Such a depository of glutamine-generating enzyme seems essential for continuous renewal of epidermal permeability barrier and during pathological processes accompanied by hyperammonemia.
Human sebaceous glands engage in aerobic glycolysis and glutaminolysis (NIH)
Background The skin and its appendages support aerobic glycolytic and glutaminolytic metabolism. Their major fuels are glucose and glutamine, which are, however, largely catabolized anaerobically.
Objectives For the human sebaceous gland it has been reported that glucose, lactate and acetate provide good lipogenic substrates but that glutamine does not. Therefore, we have investigated the intermediary metabolism in vitro of freshly isolated human sebaceous glands to determine if their metabolism of glutamine is anomalous relative to the rest of the skin.
Methods Glycolytic rate, glucose and glutamine oxidation, and glucose metabolism by the pentose phosphate pathway were determined in freshly isolated human chest sebaceous glands. Further, sebaceous intermediary metabolites were analysed using spectrophotometry and high-performance liquid chromatography. Moreover, glands were maintained in vitro as whole organs to investigate the effects of precursors and inhibitors of polyamine synthesis on rates and patterns of lipogenesis and DNA synthesis.
Results We confirm that the human sebaceous gland is a glycolytic and glutaminolytic tissue. Glucose is mainly converted to lactate, with only 6% of glucose being oxidized to CO2. Glutamine is largely converted to glutamate, alanine, serine, glycine, aspartate, threonine, lactate and ammonia, with only 12% being oxidized. We have also shown that exogenous glutamine is required for cellular proliferation and lipogenesis by human sebaceous glands. However, in its absence spermidine could fully restore rates of DNA synthesis and lipogenesis.
The induction of lipase activity in the germinating wheat grain ...by RJA Tavener - 1972 - lipase activity can be induced in the starchy endosperm by one of several nitrogenous compounds, in particular glutamine.
How much glutamine is needed?
The typical American diet provides 3.5 to 7 grams of glutamine daily which is found in animal and plant proteins. Many people are choosing to supplement daily due to the long growing list of benefits.
Research shows levels of supplementation from 2 to 40 grams daily. Two to three grams has been found to help symptoms of queasiness. This two to three gram dosage used post workout builds protein, repairs and builds muscle and can induce levels of growth hormone found in the body.
Mutagenesis and heterologous expression in yeast of a plant D6-fatty acid desaturase - Oxford Journals
Membrane-bound microsomal fatty acid desaturases are known to have three conserved histidine boxes, comprising a total of up to eight histidine residues. Recently, a number of deviations from this consensus have been reported, with the substitution of a glutamine for the first histidine residue of the third histidine box being present in the so called ‘front end’ desaturases. These enzymes are also characterized by the presence of a cytochrome b5 domain at the protein N-terminus. Site-directed mutagenesis has been used to probe the functional importance of a number of amino acid residues which comprise the third histidine box of a ‘front end’ desaturase, the borage D6-fatty acid desaturase. This showed that the variant glutamine in the third histidine box is essential for enzyme activity and that histidine is not able to substitute for this residue. In this study it is demonstrated that replacement of the glutamine residue by histidine or isoleucine in the third histidine box of the cytochrome b5-fusion ‘front end’ D6-fatty acid desaturase abolishes enzyme activity. It is also shown that mutations within and around the third histidine box reduce the activity, but do not alter the specificity of this enzyme. The experimental data therefore indicate that the consensus motif for the third histidine box of ‘front end’ desaturases should be amended to Q-X[2-3]-H-H, since substitution of this glutamine residue by histidine is not tolerated.
Inflammation rather than nutritional depletion determines glutamine concentrations and intestinal permeability.
Mutagenesis of the borage Delta-6 fatty acid desaturase in presence of glutamine.
Delta-6-Desaturase
Ge et al.] also identified human FADS2 as the major fatty acid desaturase in human sebaceous glands capable of catalysing palmitate (C16:0) D6-desaturation to sapienate (C16:1n-10). In human, sapienate is the major fatty acid in sebaceous gland. Thus these authors proposed that FADS2 plays an important role in sebum production, possibly sebocyte differentiation in human and skin homoeostasis.
Citrus Inhibits Sebum Production
General
More on Sebum from Acne Sites
Lactoferrin & Lactoperoxidase: part of a complex of enzymes derived from sugar and whey, which have a remarkable effect on the skin in helping to regulate sebum production and support the skin's natural immune system. They are a non-active ingredient with anti-microbial activity. Potassium Thiocyanate: part of a complex of enzymes derived from sugar and whey. It is a non-irritant ingredient with anti-microbial activities that work to promote normalization of skin sebum.
Moss Extract: from mosses (Phyllum Bryophyta) has sebum regulating and healing properties.
Orange Blossom Hydrosol: Hydrosols are the result of the plant material, when exposed to steam, releasing volatile therapeutic components into the water. The essential oil is drawn off and the hydrosol is left containing micro molecules of essential oil and constituents from the herbal or floral material. Orange blossom hydrosol is an effective sebum regulator for dry or combination skin.
Squalane: a light-weight oil derived from olives, wheat germ or rice bran, squalane is also found in human sebum in quantities around 10%. Hydrogenation of olive-derived squalane gives it stability and enables its use in skin care. It is a luxurious, non-comedogenic, irritation-free oil that the skin readily absorbs due to its similarity to the skin's own sebum.
Glucose Oxidase: a non-irritant active ingredient with anti-macrobial activities. It promotes normalization of skin sebum production. Excellent for acneic skin conditions; significantly reduces blackheads.
What foods help fight acne?
It's really the flip side...more colourful fruits and vegetables, whole grains. Why? These do not spike blood sugar and insulin, they keep it stable...they also carry with them lots of antioxidants that are important for skin protection in acne.
More fish and seafood. Why? Research shows that those who eat the greatest amounts of fish and seafood have the lowest rates of every type of acne blemish...from blackheads to acne cycts. The reason is almost certainly because the omega-3 fatty acids help to turn off the acne inflammation and turn down the dial on sebum production.
Drink green tea. Why? In addition to all its other health benefits, green tea has a natural antioxidant chemical that can trurn down production of an acne-promoting hormone called di-hydrotestosterone. Watch out for vegetable oils, we are currently over consuming omega-6 fats from corn, soybean, safflower and sunflower oils. Why? This type of fat can drive sebum production and inflammation right at the pore level.
http://www.outsmartacne.com/sebum/
Linoleic acid is a natural compound of sebum. Sebaceous glands, found within hair follicles, release sebum to provide lubrication of follicles and surrounding skin. The body requires these essential fatty acids, linoleic and alpha-linoleic acids, more known as Omega-3 and 6.
Studies have discovered links that propose that Trans fats may break down the body's own supply of linoleic and alpha-linoleic acids. This is why acne breakouts are more likely to appear in people that have a deficiency in Omega-3 and Omega-6 oils.
Sebum output begins to be produced with oleic acid that can cause irritation to the skin which is why acne can appear. It has been proposed that oleic acid sebum is drier, stiffer and more prone to cause blackheads, whiteheads and to shape follicular plugs which lead to blemish infections.
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