Hair Pigmentation Chemistry – The chemistry, function and source of melanin, its distribution and the consequences of its absence
Dr Svitlana Soroka MTTS 07/03/2024
INTRODUCTION
Hair pigmentation chemistry explores the intricate processes involved in determining the colour of human hair. The colour of hair is primarily influenced by pigments, with melanin being the key pigment responsible for the diverse range of hues, observed in different individuals.
Melanin, synthesized by specialized cells called melanocytes within the hair follicles, plays a pivotal role in hair pigmentation. The synthesis of melanin involves complex biochemical pathways that begin with the amino acid tyrosine. Enzymes such as tyrosinase, catalyse the conversion of tyrosine into melanin precursors, which ultimately contribute to the pigmentation of hair fibres.
Two main types of melanin contribute to hair colour: eumelanin and pheomelanin. Eumelanin is responsible for darker shades of hair, ranging from black to brown, while pheomelanin contributes to lighter shades, including red and yellow hues. The interplay between these two types of melanin, as well as their distribution within the hair shaft, determines the final colour of an individual’s hair.
Hair pigmentation chemistry is influenced by various factors, including genetic predisposition, environmental exposures, aging and overall health. Genetic factors dictate the expression of genes involved in melanin synthesis and distribution, whereas environmental factors, such as exposure to sunlight and pollutants can affect hair colour over time.
HISTORY
Melanin is a pigment found widely across the biological spectrum, from microorganisms to humans. It plays crucial roles in various organisms, including protection against harmful UV radiation, thermoregulation, and even coloration for camouflage or attraction. The term “melanin” originated from the Ancient Greek word “μέλας” (mélas), which means “black” or “dark.” This etymology reflects the pigment’s characteristic dark coloration, which is evident in its various biological forms, found across different organisms.
The history of melanin research spans centuries, reflecting humanity’s evolving understanding of biology, chemistry and medicine.
Early Observations: The presence of melanin-like substances in biological tissues has been noted since ancient times, although the nature of these substances was not fully understood. Ancient civilizations observed pigmentation in animals and humans but did not have the scientific tools to investigate melanin’s chemical composition. The first dated scientific report of the study of pigmentation, was by Italian anatomist Malphigi, in the17th century. However, it was not until the 1950s in the USA, where a more rigorous cellular and molecular analysis approach was adopted, for studying epidermal pigmentation. Notable contributions include the elucidation of the “epidermal melanin unit” and the breakdown of melanin biosynthesis (melanogenesis) pathways. Fitzpatrick and Breathnach, followed by Lerner and Fitzpatrick, made pivotal descriptions in this regard during the 1950s. Additionally, follicular pigmentation studies saw significant progress with the publication of a notable report titled “The Nature of Hair Pigment” by Fitzpatrick, Brunet, and Kukita in 1958. This report played a prominent role in Montagna and Ellis’s influential work, “The Biology of Hair Growth.” (1958) (Blume-Peytavi, 2008)
In recent decades, advances in molecular biology, genetics and biochemistry have deepened our understanding of melanin. Scientists have identified genes involved in melanin synthesis and regulation and have studied melanin’s role beyond pigmentation, including its involvement in immune responses and neuroprotection.
Overall, the history of melanin research reflects a gradual process of discovery and exploration, driven by the quest to understand its chemical structure, biological functions and medical significance.
STRUCTURE AND FUNCTION
Natural Hair Colour
To comprehend and explore the fundamental mechanisms controlling pigmentation in humans, it’s essential to examine the process systematically (Prunieras, 1986). There are four primary categories of factors that regulate mammalian melanin pigmentation:
- Factors that control the abundance and localization of melanocytes in the hair and skin.
- Factors that regulate tyrosinase and the synthesis of melanin.
- Factors that determine the structure and distribution of melanosomes within melanocytes.
- Factors that influence the transfer of melanosomes from melanocytes to keratinocytes and the dispersion of melanosomes within these cells.
Genetic and epigenetic factors play a significant role in regulating all of these stages. However, numerous diseases and environmental factors can also influence hair colour (Dawber, 1997).
In humans, melanin manifests in three forms: eumelanin, which further divides into black and brown varieties, pheomelanin red and yellow colours.
Eumelanin and pheomelanin are synthesized within melanocytes located in the basal layer of the epidermis. Melanocytes (specialized skin cells responsible for melanin production and feature extensions (dendrites) situated within hair follicles) originate from melanoblasts that migrate from the neural crest, after the closure of the neural tube. Once melanin is synthesized within melanocytes, it is encapsulated in small, spherical organelles known as melanosomes. These melanosomes are then transferred from melanocytes to adjacent keratinocytes through dendritic processes. Upon reaching keratinocytes, melanosomes are strategically positioned near cell nuclei, to shield them from incoming ultraviolet (UV) radiation (D’Alba,2019).
Differences in pigmentation are associated with the quantity, dimensions and arrangement of melanosomes, which are individual organelles containing melanin, within melanocytes.
Eumelanin is formed through a biochemical process called melanogenesis, which occurs in specialized cells called melanocytes. This process involves the oxidation and polymerization of tyrosine and dopaquinone, which are intermediates in the melanin biosynthetic pathway. The polymerization of these compounds results in the formation of eumelanin. The specific mechanisms and enzymes involved in eumelanin formation are intricate and involve several steps, regulated by various enzymes and cellular factors within melanocytes.
The formation of pheomelanin involves the conversion of tyrosine, an amino acid, into dopaquinone, a precursor molecule. Dopaquinone is further processed and undergoes a series of chemical reactions involving sulphur-containing compounds, such as cysteine, to produce pheomelanin. These reactions are catalysed by enzymes present in melanocytes, including tyrosinase and various other enzymes involved in melanin synthesis.
Melanocyte development.
During embryonic development, melanocytes originate from neural crest cells, a transient population of cells that arise from the neural tube during neurulation. These neural crest cells undergo a process called epithelial-to-mesenchymal transition (EMT), which allows them to delaminate from the neural tube and migrate extensively throughout the embryo.
As neural crest cells migrate, they populate various regions of the developing embryo, including the skin, hair follicles, and other sites where melanocytes will eventually reside. Upon reaching their destinations, neural crest cells differentiate into melanoblasts, which are the precursors of melanocytes.
The differentiation of melanoblasts into mature melanocytes involves a series of molecular events orchestrated by various signalling pathways and transcription factors. Key signalling pathways involved in melanocyte development include the Wnt, endothelin, and Kit ligand pathways.
The Wnt signalling pathway plays a crucial role in neural crest induction and migration, as well as in melanocyte specification and differentiation. Endothelin signalling is involved in melanoblast proliferation and migration, while Kit ligand (stem cell factor) signalling is essential for melanocyte survival and differentiation.
Transcription factors such as SOX10, MITF (microphthalmia-associated transcription factor), and Pax3 are critical regulators of melanocyte development. SOX10 is required for the specification and maintenance of melanocyte lineage, while MITF regulates melanocyte differentiation and melanin synthesis. Pax3 is involved in the early specification of melanocyte precursors.
Once fully differentiated, mature melanocytes reside in the basal layer of the epidermis and hair follicles. They produce melanin, the pigment responsible for skin, hair, and eye colour, through a process called melanogenesis. Melanin synthesis occurs within specialized organelles called melanosomes, which are transferred from melanocytes to neighbouring keratinocytes, where they provide photoprotection against UV radiation.
Additional factors to consider regarding the MC1R gene relate to its influence on hair colour.
The melanocortin 1 receptor (MC1R) gene in humans, located on chromosome 16, encodes a protein that plays a crucial role in determining hair colour. MC1R is primarily expressed in melanocytes.
Variations in the MC1R gene lead to different levels of activity of the receptor protein, which in turn affects the type and amount of melanin produced by melanocytes. The normal function of MC1R is to stimulate the production of eumelanin, the darker pigment responsible for brown and black hair colours, while inhibiting the production of pheomelanin, the lighter pigment responsible for red and yellow hair colours (Ito, 2011).
Certain variations or mutations in the MC1R gene result in decreased or altered receptor activity. This reduced activity leads to a shift in melanin production towards pheomelanin and away from eumelanin, resulting in lighter hair colours such as red, strawberry blonde, or yellow. Individuals with mutations in both copies of the MC1R gene, often exhibit red hair colour.
The MC1R gene is also associated with other pigmentation traits, including skin and eye colour. Variations in MC1R have been linked to increased susceptibility to sunburn and skin cancer, due to reduced protection against ultraviolet (UV) radiation.
Interestingly, some studies have suggested a potential link between MC1R gene variants, red hair colour and pain sensitivity. It has been reported that individuals with red hair, particularly those with specific variations in the MC1R gene, may have altered pain perception and increased sensitivity to certain types of pain, including thermal and mechanical stimuli, (UCI Health, 2018).
A study exploring the relationship between redheads and pain uncovered several intriguing findings (UCI Health, 2018):
- They need about 20 percent more anaesthesia to be sedated.
- They also need more local topical anaesthetics, such as lidocaine or Novocain, which is why many redheads have a fear of dentists, according to the American Dentistry Association.
- They need lower doses of pain-killing analgesics, such as opioids.
- They easily detect changes in hot and cold temperatures.
- They may be less sensitive to electric shock, needle pricks and stinging pain on the skin.
Research indicates that the MC1R gene may influence pain thresholds through its effects on melanin production and the function of melanocytes in the skin. However, the exact mechanisms underlying this relationship are still not fully understood and require further investigation.
NATURAL COLOUR CHANGES IN HAIR
Natural changes in hair colour typically occur due to various factors, including aging, genetics, environmental influences and health conditions. Here are some reasons why natural hair colours may change:
Aging: As people age, the melanocytes in the hair follicles gradually produce less melanin, leading to grey or white hair. This is a natural part of the aging process and is influenced by genetics.
Genetics: Genetics play a significant role in determining hair colour. The genes inherited from parents influence the type and amount of melanin produced by the melanocytes. Changes in hair colour may occur over time due to genetic factors.
Environmental Factors: Exposure to environmental elements such as sunlight, pollutants and chemicals in hair products, can cause hair colour to fade or change. Sun exposure, in particular, can lighten hair colour due to the breakdown of melanin pigments.
Health Conditions: Certain health conditions or medical treatments can affect hair colour. For example, hormonal changes during pregnancy or menopause can lead to changes in hair pigmentation. Medical treatments like chemotherapy can also cause hair to temporarily change colour or texture.
Nutritional Deficiencies: Deficiencies in certain vitamins and minerals, such as vitamin B12, iron and copper, can affect melanin production and lead to changes in hair colour.
Stress: While there is limited scientific evidence, some anecdotal reports suggest that high levels of stress may contribute to premature greying or changes in hair colour.
Smoking: Smoking has been associated with premature greying of hair, possibly due to the harmful effects of smoking on hair follicles and melanin production.
FUNCTIONS
Eumelanin and pheomelanin are two types of melanin pigment found in the skin, hair and eyes of humans, each with distinct functions:
Eumelanin:
Function: Eumelanin is responsible for producing dark brown to black pigments in the skin, hair and eyes.
UV Protection: Eumelanin provides protection against harmful ultraviolet (UV) radiation from the sun by absorbing and dissipating UV light, thus helping to prevent sunburn and skin damage.
Heat Dissipation: Eumelanin can also help dissipate heat, contributing to the regulation of body temperature.
Pheomelanin:
Function: Pheomelanin produces red and yellow pigments in the skin, hair and eyes.
UV Sensitivity: Unlike eumelanin, pheomelanin does not provide significant protection against UV radiation. In fact, it may even increase sensitivity to UV damage, leading to a higher risk of sunburn and skin cancer.
Associated with Fair Skin: Pheomelanin is more abundant in individuals with fair skin, freckles and light-coloured hair.
Overall, eumelanin and pheomelanin play crucial roles in determining the coloration of skin, hair, and eyes, as well as providing varying degrees of protection against UV radiation. However, the balance between these two types of melanin and their distribution in the body can influence an individual’s susceptibility to sun damage and risk of skin cancer.
The Follicular Melanin Unit
Distribution of Melanocytes
Migration from Neural Crest: During embryonic development, melanocytes originate from the neural crest, a transient structure that gives rise to various cell types, including neurons, glial cells, and melanocytes. Melanoblasts, the precursor cells of melanocytes, migrate from the neural crest to the epidermis and hair follicles during early embryogenesis.
Chemotaxis: Chemotactic signals guide the migration of melanoblasts from the neural crest to specific locations in the skin. These signals are mediated by various molecules, including growth factors, cytokines, and chemokines, which are secreted by surrounding tissues and cells.
Epidermal and Follicular Niches: Melanocytes are found in two main niches within the skin: the epidermis and the hair follicles. In the epidermis, melanocytes are located in the basal layer, where they interact with keratinocytes and contribute to skin pigmentation. In hair follicles, melanocytes are primarily located in the hair bulb and the outer root sheath.
Cell-Cell Interactions: Melanocytes interact with neighbouring cells within the epidermis and hair follicles, particularly with keratinocytes. These interactions are crucial for regulating melanocyte proliferation, differentiation, and melanin production. Keratinocytes produce signalling molecules, such as stem cell factor (SCF), endothelin-1 (ET-1) and α-melanocyte-stimulating hormone (α-MSH), which influence melanocyte function and melanogenesis.
Melanosome Transfer: Once differentiated melanocytes produce melanin pigment within specialized organelles called melanosomes, these melanosomes are transferred to adjacent keratinocytes. This transfer occurs via dendritic extensions of melanocytes, which establish contact with keratinocytes and transfer melanosomes to the keratinocyte cytoplasm. Within keratinocytes, melanosomes are distributed along the perinuclear region and contribute to skin pigmentation and photoprotection.
Distinguishing Characteristics of Follicular and Epidermal Melanin Units
Melanocytes in the hair bulb exhibit some distinctions from those found in the epidermis. They produce larger melanosomes compared to epidermal melanocytes. Additionally, follicular melanocytes demonstrate activity solely during particular phases of hair growth, specifically anagen stages III through VI. The correlation between melanogenesis and the hair cycle remains enigmatic and requires more research.
Overall, the distribution of melanocytes in the skin is tightly regulated by molecular signalling pathways, cell-cell interactions and microenvironmental cues. Dysregulation of these processes can lead to pigmentary disorders, such as hyperpigmentation or hypopigmentation and may contribute to the pathogenesis of skin diseases.
MELANIN ABSENCE DISEASES
Melanin absence or deficiency of it, in the body can lead to various conditions and diseases, including:
Albinism: Albinism is a genetic disorder characterized by the absence or reduction of melanin production in the skin, hair and eyes. People with albinism typically have very pale skin, white or light-coloured hair, and light-coloured eyes. They are also highly sensitive to sunlight and have an increased risk of developing skin cancer due to the lack of melanin’s protective effects against UV radiation.
Hypopigmentation Disorders: Hypopigmentation disorders refer to conditions where there is a partial loss of melanin in certain areas of the skin, resulting in lighter patches or spots. Vitiligo is one such disorder where depigmented patches appear on the skin due to the destruction of melanocytes.
Ocular Albinism: Ocular albinism affects the eyes specifically, resulting in reduced pigmentation of the iris, retina and optic nerve. It can cause vision problems such as decreased visual acuity, nystagmus (involuntary eye movements) and photophobia (sensitivity to light).
Skin Cancer: While melanin provides protection against UV radiation, individuals with reduced melanin production, such as those with albinism, are more susceptible to sunburn and an increased risk of developing skin cancer, including melanoma.
Hair and Eye Colour Changes: Conditions that affect melanin production can also result in changes to hair and eye colour. For example, premature greying of hair may occur due to a decline in melanin production with age or because of certain medical conditions.
Treatment and management of melanin absence diseases, primarily involve sun protection measures, to prevent sunburn and skin damage. Additionally, regular monitoring for signs of skin cancer, for those with reduced melanin and supportive care to address any associated vision problems or cosmetic concerns, should also be carried out. Finally, genetic counselling may be recommended for individuals with inherited forms of albinism or other melanin-related disorders.
REFERENCES
Blume-Peytavi, U, Tosti, A, Whiting, D A, Trueb, R, M, (2008) Hair Growth and Disorders, Spreinger-Verlag Berlin Heidelberg
D’Alba L, Shawkey M (2019) Melanosomes: Biogenesis, Properties, and Evolution of an Ancient Organelle.
Dawber R, (1997) Diseases of the Hair and Scalp, Third Edition, London
Ito S, Wakamatsu K. (2011) Diversity of human hair pigmentation as studied by chemical analysis of eumelanin and pheomelanin. J Eur Acad Dermatol Venereol.
Prunieras, M. (1986) Melanocytes, melanogenesis and inflammation. International Journal of Dermatology, 25, 62
UCI Health (2018) https://www.ucihealth.org/blog/2018/04/redheads-pain#:~:text=They%20need%20about%2020%20percent,killing%20analgesics%2C%20such%20as%20opioids. (Accessed 05/03/2024)
THE TRICHOLOGICAL SOCIETY 2004
