Based on a lecture presented to KSHI Seoul, South Korea – January 2007
The majority of mammals possess a hair coating.
The origins and significance of hair and the complex mechanisms by which its inexorable cyclical growth, loss and replacement occurs has, during recent years, provoked new levels of interest amongst scientific communities. It is however realistic to emphasize that although research is revealing material of great interest, much remains to be explained. Inevitably discussion and differences of opinion will arise. This work seeks to provide an overview of folliculo-genesis as I understand it.
Prof.Barry Stevens FTTS
Man is definitely not a naked ape. However, whereas he has lost the level of hair covering present in other primates, he has retained his scalp, beard, pubic and axillary hair. Anthropologists, Ethnologists, Sociologists etc. have provided a number of hypotheses to explain this – which I will not discuss herein. The sequence of development of foetal hair is of special interest as it provides us with a sound basis for research and valuable pointers toward increased understanding of follicular failure and disease.
We are grateful to the research scientists (past and present) world-wide, who have contributed to our current overall knowledge.
The study of the hair-follicle reveals a unique science and associated discipline.
The complete human skin has in the region of 5.5 million hair follicles of which 85000 – 145000 produce the variably programmed terminal hair-shafts of the scalp, eyebrows, eyelids. It is unlikely that these numbers change due to natural causes during the life of the individual.
Hair is morphologically a complex fibre consisting of a number of chemical components which provide its function and physical properties. The main component of the hair-shaft is a keratinous protein which is a condensation polymer of amino acids. This Keratin constitutes 60% – 95% of the hairs’ dry weight.
Hair contains water in varying quantity, lipids, pigments and trace elements.
Trace elements (mentioned later) may be present. They create the intrigue of hair mineral analysis which will be referred to later.
Follicular genesis and re-genesis are activities reliant upon stem cell activity.
Unlike muscle cells, blood cells or nerve cells, stem cells can proliferate (divide and renew themselves many times). They exist in two forms:
i) Embryonic stem cells – primitive (undifferentiated) cells that have the potential to become a wide variety of specialized cell types.
ii) Adult stem cells – undifferentiated cells found in a differentiated tissue which can renew itself and (within certain limitations) differentiate to yield all the specialized cell types of the tissue from which it originated.
The Dermal Papilla (DP) – invaginates the pilo-sebaceous-follicle (PSF) at its lowest point. Its blood supply arises from a sub-dermal arterial plexus.
Its form results from the activity of embryonic mesenchymal cells during early foetal life. Mesenchymal cells are stem cells that can differentiate into a variety of cell types.
It is thought the DP is responsible for differentiation (the process of cell development to form specialised organs) of the hair matrix epithelium. The lower section of the dermal sheath derives from the same source and is capable of recreating or repairing a part damaged dermal papilla in vivo.
Active cell division takes place in the lower bulb adjacent to the dermal papilla. These rapidly dividing cells (24 – 72 hours) are several layers deep. They have a spherical nucleus, some cytoplasm, ribosomes (possibly obtained from stem cell differentiation) and mitochondria. They are also rich in RNA (Fraser et al 1972) and as with epidermal keratinocytes they have filaments which extend from the desmosomes into the cell cytoplasm.
In cell biology, mitochondria (from Greek mitos – thread + khondrion – granule) are membrane-enclosed organelles, found in most eukaryotic cells (cells that have a well defined nucleus with nuclear membrane, membrane-bound organelles and ribosomes) sometimes described as “cellular power plants” because they convert food molecules into energy.
Proliferating cells surrounding the dermal papilla will form the hair-shaft.
Cells proliferating at the matrix periphery will form the inner root sheath. As these cells start to rise in the follicle through the suprabulbar alpha – keratin fibrils there is cytolysis (cell destruction).
• Cysteine production is evident followed by cystine disulphide cross-links (hard keratin) in the fully keratinised hair-shafts.
The inter-follicular hair-shaft
Medullary Cells – Differentiate from the matrix cells near the dermal papilla and remain somewhat spherical and larger than the thinner spindle like cortical cells. Their function is not known. Vellus and Lanugo hairs have no medulla.
Cortical Cells – Spindle like cells undergo intense protein synthesis (Parakkal 1969) producing dense alpha – keratin fibrils. There is cytolysis (cell destruction).
Cysteine production is evident followed by cystine disulphide cross-links (hard keratin) in the fully keratinised hair-shafts.
Cuticle Cells – During differentiation the cells become elongated flattened and overlap. Desmosomes are present but no – keratin fibrils. Protein synthesis occurs during keratinisation. Cysteine development is apparent.
The Inner Root Sheath (IRS)
Undifferentiated cells migrate from the peripheral matrix to form three concentric zones of the IRS Viz:
• IRS Cuticle (comprises one layer of cells) – cells form the inner zone interlocking with those of the Hair-shaft Cuticle.
• Huxley’s Layer (comprises several layers of cells) – forms the middle zone.
• Henle’s Layer (comprises several layers of cells) – forms the outer zone – cells join and overlap with the Outer Root Sheath.
The differentiation of IRS cells occurs in the following sequence:
Firstly – the Henle Layer (outer)
Secondly – the Huxley Layer (middle)
Thirdly – the Cuticle Layer (inner). It is believed that the IRS cells undergo keratinisation before those of the hair-shaft.
The Outer Root Sheath (ORS)
Surrounding and adjoining the Henle Layer is the Outer Root Sheath. Its lower aspect (1 or 2 cells thick) extends from the neck of the hair bulb where its outer cells elongate and become somewhat flattened. As it distances itself from the hair bulb toward the region of the sebaceous duct it becomes multi layered with the outer cell layer structurally similar to the Stratum Germinativum or ‘basale layer’ of the epidermis with which it is continuous (Parakkal 1969). Cell differentiation changes the structure of cells forming the remainder of both the Outer R.S. and Inner R.S. from this point. The cells enlarge, flatten, develop vacuoles and move to the surface possibly within sebaceous exudate as its vehicle.
The three forms of body hair
Lanugo hair (is foetal hair usually, but not exclusively – consider Congenital Hypertrichosis Lanuginosa).
Research suggests that skin appendages develop via a series of messages passing between the dermis and epidermis. (Kollar 1970, Sengel 1976 and Hardy 1992). Follicular embryogenesis is not fully understood but the aggregation of mesenchymal cells is seen as the essential element without which it cannot occur.
Much of our present understanding is based on observation, but new procedures utilising culture techniques and transgender animals will we hope serve to assist a greater understanding.
The first sign of follicular development is evident at week 9-12 of foetal life.
Sites: the upper lip and chin regions. Follicles develop initially from accumulations of epithelial cells with mesenchymal aggregation beneath. During this period of development the prospective ‘basal layer’ cells elongate as the columns of cells grow downwards into the dermis. Each dense column develops a concave tip which carries mesenchymal cells from which will derive the Dermal Papillae. Papillae are thought to retain the same number of cells throughout adult life. As the follicle extends further into the dermis it becomes bulbous and engulfs the dermal papilla which will derive its blood supply from within the dermis. This first stage of follicular development will have taken approximately 20 – 23 weeks.
The second stage of follicular development creates the sebaceous gland, arrector pilorum muscle, apocrine gland in specific follicles viz: the axillae, areolae, genital skin and facial regions. The lower aspect of the bulbous hair ‘germ’ will form the hair bulb matrix. The mesenchymal cells surrounding the bulb will form the dermal sheath. Active melanocytes are present.
Hair follicles are self-renewing, due to the activity of stem cells which are undifferentiated (have not changed into a recognized cell type), so they remain unchanged and proliferate for the lifetime of the organism .
Subject to certain stimuli, epidermal stem cells undergo mitosis, producing two daughter cells. One will retain the properties of the `mother’ stem cell while the other will differentiate into a T.A.Cell (Transient Amplifying Cell) capable of generating large numbers of specialized differentiated cells within the epidermis. During this process the integrity of the original stem cells which are the source of skin renewal, is maintained. The main function therefore of TA cells is to increase the number of differentiating cells produced by one division of the stem cell. TA cell activity allows the epidermal stem cells to remain quiescent in order to minimize mutations. TA cells are therefore direct descendents of stem cells in the epidermis and are responsible for tissue renewal and repair.
Epidermal stem cells exist within the bulbous region of the hair follicle where they are somewhat primitive and can respond as required to signals to regenerate the epidermis, follicles and sebaceous glands.
Adult stem cells are also found in the inter-follicular epidermis and the sebaceous gland.
Lanugo hairs are shed at about 28 – 32 weeks of foetal life to be replaced by a second coat of shorter lanugo hair covering the body – but not the scalp, which usually exhibits stronger pigmented hair-shafts. This second coat of lanugo hair is shed during the first 28 weeks of post-natal life.
In rare cases (perhaps 1 in 1000,000,000) a baby is born with its first unshed lanugo hair covering intact. This is termed as “congenital hypertrichosis lanuginosa”
Congenital Hypertrichosis Lanuginosa is a term for any excessive hair growth visible on a child at birth. This may involve the entire body having a covering of fine long hair, or be restricted to specific areas. This very rare X-linked dominant condition has been responsible for the descriptions ‘dog faced’ and ‘werewolf’. Figuera et.al (1995) have been mapping the gene responsible, which is on the long arm of the X chromosome between Xq24 – Xq27.
Causes of CHL : a secondary symptom of various syndromes associated with a genetic inheritance.
One notable Case History: In 1648, Dr Ulysses Aldrovandus documented several members of the family of Petrus Gonsalvus a native of Tenerife who had excessive body hair (Hypertrichosis Universalis) from birth. Gonsalvus married in the Netherlands, and fathered several children including two daughters a son and a grandchild with Congenital Hypertrichosis. The family was a popular object of medical research. Dr’s Felix Plater & Aldrovandus described them. The family was dubbed ‘The Family of Ambras’ after a castle near Innsbruck in which their portraits are still exhibited. Details of their lives were recorded in the 1582/83 sketchbook of Georg Hoefnagel in the Österreichische Nationalbibliothek (Austrian National Library) in Vienna.
Other cases documented since include: – In 1993, Dr Baumeister described nine of his patients with a form of hypertrichosis with a defining clinical presentation. To this he gave the name ‘Ambras Syndrome’. In one of the patients, a specific genetic abnormality was found on Chromosome 8
In 1998, a Dr Balducci described a case of CHL (congenital hypertrichosis lanuginosa) involving a different genetic defect on chromosome 8
An X-linked syndrome of hypertrichosis associated with gingival hyperplasia has been described.
The following practitioners have also reported possible variants of this disorder viz. (Beighton, 1970; Brandt, 1897; Broster, 1950; Cantu, 1982; Demikova, 1986; Felgenhauer, 1969; Freire-Maia, 1976; Gardner, 1964; Jalili, 1989; Janssen, 1945; Joest, 1984; Judge, 1991; Kint, 1985; Li, 1986; McKusick, 1992; Nowakowski, 1977; Partridge, 1987; Suskind, 1971).
Post Natal Hair –
Exists in two distinct forms : Vellus and Terminal.
Vellus hair – is fine, short and lightly or non-pigmented. It covers a large percentage of the skin. Histologically a hair is termed vellus if its diameter is less than 40µm (one micrometer = one millionth of a metre) and its length is less than 30mm.
Terminal hair is stronger, thicker, pigmented and usually medulated. It occupies the scalp eyebrows and eyelids in pre-pubertal children.
In post-pubertal adults androgenic influences change the nature of vellus hairs in other regions into terminal hair viz: pubic hair, axillary hair, beard hair.
Terminal scalp follicles are capable of converting into vellus hairs at any time. Progressive follicle miniaturisation from terminal to eventual vellus status is the cause of androgenetic alopecia associated with the presence of DHT. Lowered oestrogen levels may initiate follicular change from vellus to terminal hair production in women (hirsutism).
Structure of Hair
Mammalian hair-shafts consist of two or three concentric zones of differing cells dependent upon location viz
Medulla, Cortex, Cuticle + an Epicuticle (a very thin outer cytoplasmic membrane thickness 2.5 nm (nanometre = billionth of a metre).
Fine hair-shafts (blonde) rarely have a medulla. Increased diameter hair-shafts will usually possess a complete or broken medulla.
The Cortex – the main constituent of the hair-shaft which contains pigments, affords it elasticity and ability to bend. Cortical Cells are spindle-shaped. They produce increasing amounts of cytoplasmic filament which run parallel to the long axis of the cell and its follicle. Each Cortical cell has a diameter of 3 – 6 µm (millionths of a metre) and max. length of 100 µm.
The main structures are of closely packed macrofibrils (of paracortical cell type) – in solid cylindrical units with diameter of 0.05 – 0.4 µm (millionths of a metre) and of undetermined length. Some macrofibrils are less densely packed (orthocortical cells).
Between the macrofibrils are melanin granules + an inter-macrofibrilla matrix composed of endicuticular material + cytoplasmic organelle material.
Macrofibrils (the largest cortical fibres) are composed of spindle-shaped microfibrils (subfilaments) having a diameter of approx. 7 nm– (nanometres or billionths of a metre) which run parallel with the macrofibrils and are embedded within the inter-micro-fibrillar matrix.
Within microfibrils are filaments called protofibrils.
Protofribrils within the microfibrils consist of three polypeptide chains coiled forming an alpha helix.
The cortex contains colouring pigment (eumelanin or pheomelanin) which is genetically programmed and established in-utero.
Cortical cells (2 types) – dictate the straight or curly characteristics of individual hair-shafts.
Caucasoid hair (with a tendency to curl) – has both cell types but more paracortical than orthocortical.
Mongoloid hair (straight) – possesses paracortical cells.
Afroid hair (multi helical) – possesses significant levels of both cell types.
The Cuticle – Covers and protects the cortex. This strong outermost layer of the hair-shaft contains lamellor components (hard almost bone-like).
Its thickness depends on the number of layers of cells which may vary in number from 5 -10. Each layer has a thickness of 0.2 – 0.6 µm (millionths of a metre).
The outer layers overlap resembling roof tiles or scales, with their free edges overlapping pointing downward toward the skin. These cells are transparent – permitting colour pigments within the cortex to be seen through it. Each has an ‘outer cell membrane complex’ which is 5. – 25. nm– (millionths of a metre) in thickness enclosing the following three main zones viz:
i) The A-layer – cysteine rich zone with a constant thickness of approx. 40. nm– (nanometre = a billionth of a metre).
ii) The Endocuticle – the inner zone – 0.1 nm – thick. Its structure is irregular. The mechanism by which ‘intercellular cement or ‘protein matrix’ migrates to this part of the cell is currently unknown to me.
iii) The Exocuticle – the outer zone – 0.2 nm – thick. Its structure is irregular.
Postnatal hair-follicle growth cycle
From its initial creation in early foetal life, normal hair follicles undergo a continuous cycle of growth, regression (with hair evacuation) and re-genesis (with hair replacement). The cycle is four fold viz Anagen, Catagen, Telogen and Exogen.
Anagen Phase (Growing Phase) – cyclical anagen phase morphology (the study of its structure, configuration and development) indicates similarities with the initial in utero folliculo-genesis. The Anagen phase or active growth period follows follicular regression and re-genesis. Anagen hair grows on average 0.33 mm per day (~1cm per 28 days). The anagen phase can vary from 2 – 7 years in post pubertal adults. 80-88% of scalp follicles are in anagen at any time. 50% of pubic hair follicles are in anagen at any time. 44% of leg hair-follicles are in anagen at any given time. 38% of arm hair-follicles are in anagen at any given time.
Catagen Phase (Transitional Phase) – a complex stage of the follicular cycle lasting for approximately fourteen days during which mitotic activity and melanisation cease, keratinisation of the hair-shaft continues and the bulb develops a club shape as it travels upward away from its dermal papilla. The lower part of the Outer Root Sheath undergoes degeneration as the base of the follicle moves upward to lie at the level of the arrector pili insertion. The inner root sheath undergoes disintegration. Approximately 12% of scalp terminal hair-follicles are in catagen at any one time.
Telogen Phase (Resting Phase) – the follicle resting phase lasting twelve – sixteen weeks. During this time the club is held within a sac of epithelial tissue. The dermal papilla which is still connected to the base of the follicular epithelium having lost its blood supply and extra cellular matrix during Catagen appears as a ball of cells in the telogen follicle. With folliculo-regenesis and appearance of the replacement anagen hair-shaft the telogen hair-shaft is expelled form its follicle (Exogen). Each day 40 – 130 telogen scalp hair shafts are shed in this way.
Eyebrows gain length at 0.15 cm per day an achieve a maximum length of 1 cm. Eyelashes gain length at 0.15 cm per day and achieve a maximum length of 1 cm. Beard hair gains length at 0.40 cm per day.
Exogen – hair-shafts are evacuated.
Lost hair-shafts – points of interest
Hair epilated in the anagen phase would have its inner and outer root sheath material attached at its proximal end.
Telogen hairs have a tiny club end which may be almost imperceptible. No living tissue is attached.
Catagen hairs normally have a tapered proximal end.
The differentiation of catagen from telogen hairs, may require staining with 4-di-methyl-amino-cinnam-aldehyde. This dye stains Citrulline (a protein in the root sheath) red. Citrulline is considered a non-essential amino acid synthesized in the intestinal tract from Glutamine. Its function in the hair sheath is currently not understood.
General hairshaft characteristics – relative to the three true hair classes. However these are dissipating into an ever-increasing number of subclasses.
Mongoloid (oriental) hair-shafts – are thickest and coarsest, usually straight and have a circular cross section . Hair follicles number 90,000-120,000. Follicles are large and straight with a circular cross section.
Caucasoid hair-shafts – can be straight, wavy or curly. The hair follicle is circular oval or kidney shaped in cross-section. The number of follicles ranges between 86,000 -145,000. Titian haired people have 86.000 + follicles. Brunettes have 100,000 + follicles. Black haired people have 110,000+ follicles. Blondes (fine haired) have 145,000+ follicles.
Afroid hair-shafts – have tight helices. In cross section hair-follicles are elliptical or can be almost ribbon-like flat in cross section. Follicle numbers range between 50,000 – 110,000.
Chemical composition of Hair & Hair-Follicles
Hair is composed of amino acids, lipids and trace elements.
Amino acids 18 of the 20 amino acids encoded (by DNA) form the protein Keratin.
Note: Cystine is derived from the amino acid Cysteine
Lipids – nothing of significance to introduce.
Trace elements – have been identified in hair; these could be environmental or cosmetic contaminants
(e.g. As, K, Cd, Cr, Cu, Fe, Hg, I, Mo, Na, Pb, Se, Si, Ti, W, Zn), or part of the metabolic process e.g. from matrix, papilla, sebaceous and eccrine and apocrine glands.
Although this procedure is in popular usage in the America’s it has suffered criticism elsewhere. Scientists are aware of a relationship between minerals, trace elements and health and Hair Mineral Analysis employs techniques to test for the presence of these and other minerals and toxic metals in human hair samples. Hair mineral analysis is a screening test, which measures the mineral content of hair and therefore the body’s tissues. A mineral abnormality within the hair usually indicates a similar abnormality within the body.
Nutritional physiology takes place at cellular level, not within blood or other location. Is what you eat reaching your body cells. Tissue mineral analysis provides information regarding cellular activity and nutritional metabolism.
Mineral levels are locked into formed hair shafts, so analysis identifies concentrations that have accumulated in the hair during the preceding twelve – sixteen weeks.
Toxic and nutrient elements may be thus identified and measured. The process is not considered a stand-alone diagnosis and should be used in conjunction with other laboratory tests (e.g. blood and urine).
Hair analysis indicates individual deficiencies or excesses and the presence of toxic metals. The test highlights any biological antagonism that exists between certain nutrients. Vitamins cannot function or be assimilated without the aid of minerals. The body cannot manufacture minerals.
Every living cell depends on minerals for proper function and structure. composition of body fluids, blood, bone, nerve function, muscle tone including that of the cardiovascular system.
Approximately seventeen minerals are essential in human nutrition. Minerals function as co-enzymes, enabling the body to perform its functions, including energy production, growth, and healing.
Enzyme activities involve minerals, which are essential for the proper utilization of vitamins and other nutrients.
Minerals coexist with vitamins. Some B-complex vitamins are absorbed only when combined with phosphorus.
Vitamin C greatly increases the absorption of iron.
Calcium absorption requires vitamin D.
Zinc assists in the release of vitamin A from the liver.
Some minerals part of vitamins: Vitamin B1 contains sulphur and B12 contains cobalt.
Minerals are naturally occurring elements.
Rock formations consist of mineral salts. Rock and stone are gradually broken down into tiny fragments by erosion. Soil is teeming with microbes that utilize tiny crystals of mineral salts, which are then passed from the soil to plants. Herbivorous animals eat the plants. We obtain these minerals by consuming plants or herbivorous animals.
Minerals are stored primarily in the body’s bone and muscle tissue; it is possible to develop mineral toxicity if excessive quantities are consumed. No one mineral can function without affecting others.
Hair & Hair Follicle Chemistry:
• The following enzymes are present (the majority of which have unexplained significance) viz: Acid phosphatase, Aldose, Aminopeptidase, Anhydrase, Arginase, Alkaline phosphatase which is present at the basement membrane and periphery of the dermal papillary cells), Cytochrome oxidase, Carbonic anhydrase, Glucose-6-phosphatase, Esterases, Succinic dehydrogenase.
• Cysteine and Cystine – The presumptive (early developing) hair-shaft, cuticle and cortex contain cysteine sulphydryl groups which become cystine disulphide cross-links (hard keratin) in the fully keratinised hair-shafts.
• Nucleic acids – present in nuclei of dermal papillary cells.
Hair colour – determined by the presence of melanin in the cortex. Melanin is a water-insoluble polymer of compounds derived from the amino acid Tyrosine which is located within the melanocytes . The cuticle is transparent so the pigment in the cortex is visible.
Melano-synthesis may produce :
Eumelanin – formed by the reaction of the enzyme tyrosinase with the amino acid tyrosine . It produces hair colours varying between reddish brown – black.
Phaeomelanin – formed by the reaction of the enzyme tyrosinase with the amino acids tyrosine and the sulphur rich cysteine. This produces hair colours varying from yellow blonde) to red (titian).
Variations in pigmentation relate to the number, size and distribution of Melanosomes (single melanin containing organelles) within the Melanocytes. These are specialised skin cells producing melanin and having branches (Dentrites) located within hair follicles through which tiny pigment granules are injected into the keratinocytes during hairshaft genesis.
Melanin affords some skin protection by absorbing ultraviolet radiation.
Tyrosinase inactivity > nil melanogenesis = pigment free hair.
Grey hair is a illusion created by the blend of white and coloured hairs.
Elasticity of the Hair:
Hair has elasticity (the ability to stretch and return to its original status). Elasticity increases when hair is wet. Hair has been shown to stretch up to 20% of its original length before breaking when dry, and up to 50% before breaking when wet
Tensile strength of Hair:
The tensile strength of hair is measured by the force needed to break it. There are a variety of specialised devices available.
A single mongoloid hair-shaft in its virgin state may have a tensile strength equal to copper wire of the same diameter.
A dry virgin hair-shaft can withstand weights of up to 200 gm. – the total scalp hair held together as a plait can support the entire body weight without causing damage.
Tensile strength reduces when a hair-shaft is cold-water wet and further reduces with high temperature water. Research figures claim that other contemporaneously harvested hair-shafts demonstrated higher levels of tensile strength following immersion in Glycerine or Almond oil. Individual hair shafts will however sever if a sudden violent jerking force is applied.
Porosity and Hair
Liquids can pass between the cuticle scales and the cortex. The porosity of hair depends upon the condition of the cuticle. All procedures employing chemical oxidation will affect the cuticle to some extent and thereby cortical porosity will increase.
Water and Hair:
Water temporally affects the strength of hair-shafts by breaking the Ionic (salt) bonds and Hydrogen bonds of the alpha-helices. Relative humidity is the measurement of water in the air at a certain temperature expressed as a percentage of the maximum amount of water the air can hold (saturation).
With increased relative humidity (RH) hair shaft diameter may potentially increase by up to 14% – such swelling occurring between the microfibrils. Increases in length along the axis can be up to 2 %.
Hair-shafts change in response to exposure to excessive pH levels. At strong acidic levels (pH 3 -1) hair-shafts swell slightly, in strong alkali levels (pH over 10) hair-shafts can swell excessively to beyond the point of severance e.g. trichorrhexis nodosa.
The Trichological Society