NATURAL HAIR COLOURING
Hair colour is genetically programmed and established in-utero.
Hair colouring relates to the presence or absence of melanin.
Pigmentation is due to the presence of Melanin a water-insoluble polymer of compounds derived from the amino acid Tyrosine which is located within melanocytes.
Melanosynthesis 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 (titians).
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 hair shaft genesis.
Melanin affords some skin protection by absorbing ultraviolet radiation.
Tyrosinase inactivity > nil melanogenesis = possible Albinism.
Titian Hair MC1R and pain thresholds
In 2000 scientists identified the gene responsible for titian hair – MC1R (Melanocortin 1 Receptor) protein which is involved in skin and hair colour regulation.
Carriers of a mutated version of MC1R have a 1/64 chance of parenting a child with titian hair, pale skin and blue eyes.
It is suggested that MC1R mutation releases a hormone in the brain which mimics endorphins. Endorphins have several functions one of which provides pain relief. This may affect how the body receives pain signals from the brain. Consequently red heads may need smaller does of certain pain killing drugs.
© 2000 – B Stevens FTTS
Hair Pigmentation Chemistry
Dr Idalina Fialho
Human hair is comprised mainly of protein, at 65−95% by weight. Keratin, the most abundant component, is a group of insoluble protein complexes which impart elasticity, suppleness, and resistance to the fibers. Melanin, nature’s hair pigment, is mainly distributed in the middle layer of the hair shaft or cortex and is embedded between keratin fibers, where it makes up only 1−3% of human hair by weight. These nanometer-scale granular pigments (200−800 nm) generate the naturally beautiful colors found in human hair. Colors arise from the distribution, concentration, and blending of two types of melanin: brown and black eumelanins, and less commonly, red pheomelanins. It follows then that the reduction or disappearance of melanin from hair fibers is the phenomenon that leads to color loss and consequent hair greying and eventually whitening. Hair whitening is mainly caused by aging, although the regulation of hair pigmentation and pigment concentration can be affected by numerous factors including metabolism, hair- cycle changes, body distribution of melanins, gender differences, and the use of medicines (e.g., chemotherapy), or by specific genetic disorders. Taking these factors into account, the average age for white hair onset is mid-30s, with 50% of people exhibiting 50% gray hair by the time they are 50 years of age. The first known example of natural hair dye dates back to the ancient Egyptians when henna plant pigments were used for hair darkening and color reinforcement. Dye technologies are at the very origin of the chemical industry, with the first artificial “long lasting” hair dye synthesized by L’Oreál founder Eugeǹe Schueller in the early 1900s. Since then, hair dyes capable of providing a long lasting and convincing gray to black transition have become popular across cultures and nationalities, with additional colors, including those beyond one’s genetic predisposition, desirable. Because of such widespread use, hair dye industries are now among the most profitable in the cosmetics sector. As a matter of fact, studies suggest that over 50% of the population in developed countries has dyed their hair at least once in their life. Despite several studies reporting the potential carcinogenicity of certain conventional hair dye components, frequent development of allergies in clients and colorists, and dye-induced hair damage, the use of small molecule-based dyes in modern society continues to expand, and the industry has made only few minor advances in its chemistry.
Melanin is the generic name used to refer to perhaps the most ubiquitous, resistant, heterogeneous, and ancient pigments found in nature. Melanin appeared very early in most living kingdoms on the Earth. The name “melanin” comes from the ancient Greek melanos, meaning “dark,” and, according to Borovansky, the term was probably first applied by the Swedish chemist Berzelius in 1840 to call a dark pigment extracted from eye membranes. However, first references of human skin pigmentation and somehow to the existence of melanin without using the current name are very old. Pharaonic medicine in the Ebers Papyrus (1550 BC) described some diseases affecting skin color, and one of them was probably vitiligo, although that term appeared much later, derived from the Latin word “vitellus” meaning “veal” or pale pink skin. The first relatively detailed written description on skin pigmentation in mankind came from Herodotus in Greece, who described the darker skin of Persians, Ethiopians, and Indians in relation with Greeks. In the modern era, there were a great number of anatomical descriptions by eminent scientists of those centuries, such as Malpighi in Naples and many others. In those centuries, the most common idea in Europe and the Arabic civilization about the origin of the dark pigment was that it was derived from the decomposition of hemoglobin. The first chemical analyses by Berzelius and others established very significant differences between melanin and hemoglobin, making it unlikely or ruling out such relationship. Structurally, melanins are a group of complex pigments with a structure relative diverse and undefined. They have been defined in several ways during the last 50 years but most of the proposed definitions present some small pitfalls as they are partial or uncompleted due to the difficulty of defining something with such a wide diversity in composition, color, size, occurrence, and functions. This is obvious since melanin can be found in all living kingdoms. A widespread and simple definition to include all types of melanin would be “heterogeneous polymer derived by the oxidation of phenols and subsequent polymerization of intermediate phenols and their resulting quinones.”
Melanin is present in mammalian skin, hair, eyes, ears and the nervous system. It is known to exist in birds’ feathers, squid’s ink, insects, plants and many other biological systems. Recently, it has received considerable attention and research. Melanin is abun-dant in many human diets, but no research has been attempted to evaluate effects of daily intake.
Classification of melanin
Melanin is classified into three groups: eumelanins, pheomelanins and allomelanins. Melanins of the nervous system are known as neuromelanins. Colours of the eumelanins, which are most commonly found in animals, are black or brown. They are highly insoluble pigments that form with in specialized cells known as melanocytes. Enzymatic action of the enzyme tyrosinase on the amino acid tyrosine produces melanin. In their primary biosynthetic pathway, tyrosine is hydroxylated to form the catecholamine 3,4-dihydroxyphenyla-lanine (DOPA), which is then oxidized to form 3,4-dioxyphe-nylalanine dopaquinone) before cyclization to 5,6-indolequinones and their subsequent polymerization to form melanin. Similar to the biosynthesis of eumelanin, melanin known as pheomelanin is biologically synthesized, except that a precursor containing sulphur is incorporated in the structure. Eumelanin is usually observed as brownish to dark black colour of the skin and hair, while pheomelanins are reddish and yellowish in colour. Many biological systems produce a combination of the two types of melanin. Red-haired people usually have more of pheomelanin in their hairs and skins. Many studies have shown that people with pheomelanin as the predominant pigment are susceptible to more photodamage than people with predominant eumelanin in their skins. The importance of melanin as a vital biological molecule is well recognized. It has even been suggested that melanin has played an evolutionary role as a central ‘organizing molecule’, assuming functions similar to those of enzymes in present evolutionary systems. Despite this recognition, many of the Mini Review basic functions of melanin remain poorly understood.
As melanin is located in many animal tissues, and in practically all living organisms, it is not surprising that melanin has a lot of different functions. Most of these functions are related to protection against external insults and to confer environmental advantages to melanized cells.
It is clear that skin melanin is a very efficient photoprotective factor; melanin is a natural sunscreen that functions as a broadband radiation absorbent. Thus, melanin prevents the skin from the potentially damaging effects of UV light. Exposure of human epidermis to sunlight produces melanin, causing a moderate tan effect on the skin to increase the amount of photoprotective pigment. Many epidemiological studies have shown a lower incidence for skin cancer in individuals with high amount of melanin in the skin. Skin is the most common site of cancer in humans, especially in those with pale skin, and UV is the main environmental factor responsible for the formation of malignant melanoma and other skin cancers. Both eumelanin and pheomelanin are affected by sunlight, and they form semiquinoid-type free radical species and then typical free radical species from water, but eumelanin is quite stable and large enough to scavenge the originated species. In contrast, pheomelanin has been shown to be rather photolabile under sunlight at physiological conditions, and it is easily involved in the high production of superoxide. It cannot scavenge all the derived reactive species, and thus, pheomelanin may easily become a photosensitized agent rather than a photoprotector. Given the phototoxicity and the reported capacity to increase cancer risk of pheomelanin, this point is especially relevant for pale-skin individuals. Albinism is an autosomal recessive genetical disorder characterized by the incapacity to produce melanin. Taking into account the photoprotective function of cutaneous melanin, it is obvious that these patients are very sensitive to sunlight, as their skin, hair, and eyes miss the protector pigment.
Aside the photoprotection of cutaneous melanin, many other functions should be considered. Melanin, especially eumelanin, is an insoluble, resistant, and stable biopolymer, without significant degradation, and thus it is sometimes considered as a relatively inert substance, but this is not really correct. Melanins are quite reactive, and they display a series of complex structural and physicochemical properties in addition to resistance to degradation. They present charge-transfer redox activity, and they are outstanding stable radical, free radical scavenger, chelating agent for ions, binding capacity for a variety of biomolecules, and organic agents (drugs, antibiotics, and other xenobiotics). These chemical properties make melanins beneficial pigments in many ways different from sunlight absorption as they can act as (a)redox polymers, buffering the level of other intracellular redox biomolecules inside the cell; (b)radical scavengers, for the neutralization of ROS and other reactive oxygenated species; (c)ion chelating agent and possibly exchanger; melanin is able to chelate metal ions through its carboxylated and phenolic hydroxyl groups, in many cases with high affinity and efficiency; thus, it may serve to sequester potentially toxic metal ions, protecting the rest of the cell; (d)polymers with strong capacity to bind a variety of organic molecules, xenobiotics, and aromatic and lipophilic compounds; (e)a protection shield for encapsulating and isolating structures, such as fungal spores, reinforcing cell walls and insect exocuticle; (f)semiconductor materials with high capacitance useful for nanotechnological devices.
Concerning extracutaneous animal melanins, in the eye, melanin seems to modulate the incidence of beams of light entering the eye and the RPE (retinal pigment epithelium) attached to the retina. Melanin would absorb scattered light within the eyeball, allowing greater visual acuity. The pigment at the iris and choroid also helps to protect retina from intense sunlight. In agreement with that, people with blue or green eyes are more at risk for sun-related eye problems, and albinism greatly affects visual acuity. In turn, melanin in the RPE shows antioxidant properties, protecting components of RPE such as A2E from photooxidation. This ability appears to decrease in humans as they grow older. Finally, as a totally new but different application of ocular melanin, iris melanin provides a rich light imaging very promising for personal identification by iris recognition.
The presence of melanin in the inner ear was established more than a century ago, but the exact biological function of the pigment in the labyrinth has yet to be determined. It has been proposed that high frequency or intensity acoustic waves could be buffered by melanin to regulate otocytes reception and appropriate hearing. Alternatively, melanin may also function as a biological reservoir for divalent ions and as an ion exchanger, as well as an intracellular buffering system for calcium homeostasis. Supporting that function of cochlear melanin, in humans, hypopigmentation and deafness occur together in the rare Waardenburg syndrome. The absence of melanocytes in the stria vascularis of the inner ear results in cochlear impairment, although the mechanisms for that effect are not well understood.
The function of neuromelanin in the human substantia nigra is a very interesting and intriguing issue, as other mammals have no neuromelanin in the brain. It is believed that neuromelanin is also a protective molecule in the brain. In the same way that UV radiation creates an oxidative stress in the skin, the aerobic metabolism of catecholaminergic neurons can also generate a number of o-quinones, such as o-dopaminequinone and oxygen reactive species, due to the catecholic nature of the occurring neurotransmitters. Exposure to traces of heavy metals, especially ferric ions , released from neuronal tyrosine hydroxylase or mitochondrial cytochromes, is also a stress factor, as this metal ion generates redox cytotoxic reactions, as the Fenton reaction. It is clear that these threats should be mitigated, and melanin seems to be a very appropriate molecule to scavenge ROS and to chelate metal ions. In turn, neuromelanin can be formed “in situ” from the catecholic neurotransmitters, once they have been oxidized and are not useful as neurotransmitter anymore. In Parkinson’s disease, there is a decrease in neuromelanin in the substantia nigra as a consequence of specific dropping out of dopaminergic and noradrenergic neurons. Moreover, the loss of neuromelanin observed in Parkinson’s disease is accompanied by an increase in iron levels in the brain. In agreement with those considerations, a dual role for neuromelanin in the pathogenesis of that disease has been proposed. On the other hand, neuromelanin should been considered as a neuroprotective agent, but it is also a molecule which accumulates a variety of potentially damaging species and also drugs such as amphetamines and MPTP, so that this accumulation in the brain can also become a thread for neurodegeneration. In that way, neuromelanin is as a double-edged sword and currently is an issue of active research.
The Follicular Melanin Unit
Distribution of Melanocytes
In active hair follicles, melanocytes characteristically occur in the wall of the pilary canal (infundibulum) and in the pigmented part of the bulb, close to the upper part of the dermal papilla. Usually, no active melanocytes are observed in other locations. However, dopa-positive melanocytes have been observed in the outer root sheaths of hair follicles after
irradiation with X-rays, after dermabrasion, after exposure to ultraviolet rays, and after oral photochemotherapy. Amelanotic melanocytes (dopa-negative) have been observed along the outer root sheath of the middle and lower part of the follicle, between the basal portion of the tall epithelial cells that form the outer peripheral layer. Concerning the distribution of these active and inactive melanocytes, Staricco divided the hair follicle into four parts. Portions A and D, melanotic portions, constitute, respectively, the upper part of the follicle (infundibulum) and the upper part of the bulb in contact with the upper papilla. Portion B comprises the middle and lower follicle and possesses amelanotic melanocytes. Portion C is the generally amelanotic outer root sheath of the bulb and the hair matrix below Montagna’s critical level.
Distinctive Features Between the Follicular and Epidermal Melanin Units
Hair bulb melanocytes differ from those in the epidermis only in some respects. They synthesize larger melanosomes than the epidermal melanocytes. Follicular melanocytes are active only during a specific phase of hair production, namely anagen stages III through VI. How melanogenesis is linked to the hair cycle is a mystery. When epithelial mesenchymal interactions during mammalian hair follicle development are better understood, it is likely that many questions related to hair melanin pigmentation will be solved.
The Melanocyte Population of the Skin as a Bicompartmental System
Several clinical situations suggest that the epidermal and follicular compartment of the melanocyte population of the skin are relatively independent. Senile white hair often occurs on a scalp epidermis with a normal melanin pigmentation. On the other
hand, body hairs often keep their normal color in a fully depigmented lesion of vitiligo. It is clear, however, that exchanges may occur between these two compartments, which are not closed systems. This has been demonstrated under certain circumstances in
which one of the two melanocyte compartments is altered or destroyed. After dermabrasion (removal of the epidermis and the infundibulum follicle), amelanotic melanocytes divide in the middle portion of the hair follicle, become active (dopa-positive), and migrate upward from the outer root sheath to the infundibulum and
later into the basal layer of the healing surrounding epidermis. A similar process occurs during epidermal wound healing after pure epidermal destruction by suction (Ortonne et al, personal observation). Evidence for such exchanges has also been obtained from the
study of repigmentation of vitiligo skin during oral photochemotherapy.
After destruction of hair melanocytes by various physical agents (X-ray, freezing, etc.), regenerated hair follicles remain depigmented, giving rise to white hair. Few experiments suggest that such exchanges exist. In the guinea pig, an autograft of full-thickness black skin left for 7 d in white skin, later removed, is followed by the appearance of pigmentation due to active melanocytes in the healing wound. Within a few months, white hair grows as well as black haiR. This may be due either to the persistence in the wounds of pigmented hair bulbs from the graft, or to migration of isolated melanocytes from the pigment grafts that colonize the regrowing white hair bulbs. In humans, after induction of a pure dermal wound, removing the middle and lowest portion of hair follicles, regrowing hair is still pigmented. It is possible that the melanocytes present in this hair originate from the overlying epidermis.
Melanogenesis in Hair
Human Red Hair
In human red hair, specified as pheomelanic by chemical analysis, melanocytes contain spherical melanosomes with microvesicular (vesiculoglobular) and proteinaceous matrices on which melanin deposition is spotty and granular.
In other human red hair specified as “mixed” type melanogenesis by chemical analysis, many of melanocytes produce spherical melanosomes of pheomelanic form. They also contain “mosaic” melanosomes with features of both eumelanosomes (ellipsoidal shape, regular striation) and pheomelasomes (spotty and microgranular melanization, lack of electron- lucent bodies in mature melanosomes). The nature of these “mosaic” melanosomes, whether they are eumelanic, pheomelanic, or mixed, remains to be clarified.
Human Blond Hair
Since the identification of pheomelanosomes, few detailed electron microscopic studies of human blond hair follicle have been reported. Melanin granules are smaller and less numerous in blond than in dark-haired subjects. Melanosomes are not fully melanized even in the dendritic processes of melanocytes. This suggests that the light color in blond hair may be due to a quantitative decrease in the production and melanization of melanosomes.
Human Black and Brown Hain
Typical ellipsoidal melanosomes, at various stages of melanization, are observed in follicular melanocytes of black hair. Their ultrastructural characteristics are identical to those seen in the epidermis of caucasoids and negroids. Melanosomes transferred to neighboring keratinocytes are singly distributed. In brown hair, the follicular melanocytes also contain all the developmental stages of eumelanosomes. Lighter brown hairs have smaller melanosomes. Similar aspects are observed, whatever the racial background.
Senile Gray and White Hairs
In the melanocytic zone of the senile gray hair bulb, the number of melanocytes appears normal or reduced. These cells show little melanogenic activity and contain very few melanosomes. In senile white hair, there are no dopa-positive melanocytes. By electron microscopy, melanocytes are scarce or entirely absent and there is no melanin in the matrix and cortex. Similar findings have been observed in white hair from vitiligo macules. The senile white hair-bulbs do not contain immunoreactive tyrosinase antigen. More recently, tyrosinase mRNA or its protein have been detected in senile white hairs, suggesting the presence of amelanotic melanocytes within the outer root sheath.