SKIN PIGMENTATION Rajiv Rakshit*, Shubhrajit Mantry, Sudip Das, Himalayan Pharmacy Institute, Majhitar, Rangpo, E. Sikkim 737136, INDIA ARTICLE INFO: Article history: Received: 1 August 2016 Received in revised form: 11 September 2016 Accepted: 01October 2016 Available online: 10 November 2016 Corresponding Author: Rajiv Rakshit, Himalayan Pharmacy Institute, Majhitar, Rangpo, E. Sikkim 737136, INDIA Email: rajivrakshit1996@gmail.com Phone: +91 9093367405 Abstract The human skin colour is an easily noticeable trait and is very often used as a measure of differentiation among people. Our skin complexion draws the attention of human eyes very easily. Now, with developing knowledge it is not unnoticed that the variation in skin colour highly arises due to change in latitude. The pigment present in our skin is an organic polymer called as melanin synthesized by our skin itself. Melanin is not only responsible for regulating our skin colour but also for factors like freckling and hair colour. In this article we will understand the relationship between the development of skin colour and various factors like UV radiation, folic acid and vitamin D3. We will also understand the relationship between skin pigmentation and cancer and how our skin colour helps in our survival. Further, we will also discuss about skin whitening and ways to minimize the synthesis of skin pigment by use of various chemical substances which would affect the process of melanogenesis at various steps. Key words Skin, Melanin, Melanogenesis, UV radiation, Vitamin D3 INTRODUCTION It has always been a mystery to the biologists as to what is the reason behind different skin complexion of different individuals. Variation in skin color is the most noticeable of human polymorphisms. As visually dominant mammals, we readily notice differences in skin color in each other. As primates who uniquely use language to create categories, we readily give names to these th differences. Since the mid 18 century, skin color has been the single most important physical trait used to define human groups, including variously named varieties, races, subspecies, and species. Charles Darwin observed variation in human skin color while abroad during the voyage of the H.M.S. Beagle (1831 1836), but he soundly rejected the notion that physical differences such as skin color constituted the basis for distinguishing separate human species. Melanin is a group of natural pigments found in all the living organisms except Arachnids (Arthropods belonging to class of Arachnida) which is responsible for the skin pigmentation. Melanin is an organic polymer produced by the oxidation of amino acid tyrosine by enzyme tyrosinase, followed by polymerization [1]. The pigment is produced in specialized cells called melanocytes by the process of melanogenesis. There are three basic types of melanin: eumelanin, pheomelanin and neuromelanin. The most common is eumelanin which has two types-brown eumelanin and black eumelanin. Pheomelanin is a cysteine containing red polymer of benzothiazine responsible mainly for red hair. Neuromelanin is found in brain, though its function is not known [1]. The characteristic phenotype of fair skin, freckling, and carrot-red hair is associated with large amounts of pheomelanin and small amounts of eumelanin and is caused by loss of function alleles in a single gene, the melanocortin 1 receptor (MC1R) [2]. In the skin, melanogenesis occurs after exposure to UV radiation, www.ujpsr.com 42
SHORT COMMUNICATION ARTICLE causing the skin to tan visibly (Drakened skin colour). Melanin is an active absorber of light, the pigment is able to dissipate over 99.9% of absorbed UV radiation [1, 3]. Because of this property, melanin is thought to protect skin cells from UV-B radiation damage, reducing the risk of cancer. Furthermore, though the exposure to UV radiation is associated with increased risk of malignant melanoma, a cancer of melanocytes, studies have shown a lower incidence for skin cancer in individuals with more concentrated melanin i.e., darker skin tone [1]. The Fig.1: Melanin biosynthesis of melanin takes place in specialized cells called melanocytes, within membrane bound organelles called mealnosomes. Melanosomes are transferred via dendrites to surrounding kerationcytes. Keratinocytes and melanocytes are collectively known as 'the epidermal melanin unit'. Each melanocyte is in contact with approximately 40 keratinocytes in the basal and super basal layers. Melanocytes are deposited in the epidermis hair follicle, the inner ear and eye [4]. Fig.2: Melanin boisynthesis flowchart [5]. Varying Skin Colour People vary in their skin tone due to differences in the distribution, quantity, size, and type of melanin found in their skin cells. As you might suspect, people with dark skin tend to have larger and more numerous melanincontaining particles in their skin. This provides protection from the sun's UV rays. Many genes are known to affect the production of melanin and cause skin color variation in humans. While skin color is an inherited characteristic, the fact that many genes code for this trait explains why children do not always exactly match their parents' skin tone [6]. For the same body region, light and dark skinned individuals have similar number of melanocytes but pigment containing organelles, called melanosomes, are larger, more numerous and more pigmented in dark compared to intermediate compared to light skin. Relationship of Skin Colour to Latitude Credit for describing the relationship between latitude and skin color in modern humans is usually ascribed to an Italian geographer, Renato Basutti, whose widely reproduced skin color maps'' illustrate the correlation of darker skin with equatorial proximity. More recent studies by physical anthropologists have substantiated and extended these observations; a recent review and www.ujpsr.com analysis of data from more than 100 populations found that skin reflectance is lowest at the equator, then gradually increases, about 8% per 10 of latitude in the Northern Hemisphere and about 4% per 10 of latitude in the Southern Hemisphere. The pattern is inversely correlated with levels of UV radiation which are greater in Southern than in the Northern Hemisphere [2]. 43
Fig.3: (A) Human skin colour distribution throughout the world (B) Relationship of skin colour to latitude [7] The figure (A) depicts the traditional skin colour map by Biasutti and Figure (B) shows the relationship between latitude and the average skin reflectance of populations located throughout the world. The normally hypothesized theory reveals that with increase in latitude skin becomes lighter i.e., dark skin towards the equator and lighter skin towards the pole. Statements regarding the number of human skin color genes are attributed to several studies, one of the most complete study is by Harrison and Owen (1964). In that study, skin reflectance measurements were obtained from 70 residents of Liverpool whose parents, grandparents, or both were of European ( with a large Irish component'') or West Evolution of Skin Colour Based on all the information it can be hypothesized that darker skin evolved to protect against the harmful effects of UV light. Individuals who lacked optimal pigmentation for tropic latitudes had a greater risk of skin cancer and death. But recent studies show some serious problem with this hypothesis. Human skin pigmentation is the product of two clines produced by natural selection to adjust levels of constitutive pigmentation to levels of UV radiation (UVR). One cline was generated by high UVR near the equator and led to the evolution of dark, photoprotective, eumelanin-rich pigmentation. The other was produced by the requirement for UVB photons to sustain cutaneous photosynthesis of vitamin D3 in low- UVB environments, and resulted in the evolution of depigmented skin [8]. The fact was always overlooked by the scientific community that dark skin has evolved as protection against skin cancer. In 1991, the anthropologist Nina Jablonski was skimming through African ( mostly from coastal regions of Ghana and Nigeria'') descent and who were roughly classified into hybrid'' and backcross'' groups on this basis. An attempt to partition and analyze the variance of the backcross groups led to minimal estimates of three to four effective factors,'' in this case, independently segregating genes. Aside from the key word minimal one of the more interesting findings was that skin reflectance appeared to be mainly additive. In other words, mean skin reflectance of F1 hybrid'' or backcross hybrid'' groups is intermediate between their respective parental groups [2]. scientific journals when she came upon a 1978 paper by Branda and Eaton. This paper investigated the effects of sunlight on an essential chemical found in our body: folate or folic acid (one of the B vitamins). Folate is an essential nutrient for DNA synthesis. Since cells reproduce at a fast pace during fetal development (and hence, there is a lot of DNA replication), the highest levels of folate are needed during pregnancy. Folate can explain why dark skin evolved, but it cannot account for the evolution of light skin. Vitamin D3 is essential for normal growth, calcium absorption, and skeletal development. It is particularly important in maintaining and repairing healthy bones and teeth. Its role in calcium absorption makes it essential in maintaining a healthy heart, blood clotting, a stable nervous system, and an effective immune system. Deficiencies manifest themselves as rickets (softening of the bones), osteoporosis, and osteomalacia. It can lead to death, www.ujpsr.com 44
SHORT COMMUNICATION ARTICLE immobilization, or deformities. Women have a higher need for this nutrient during pregnancy and lactation due to their need to absorb calcium to build the fetal skeleton. Humans can obtain vitamin D3 by one of two means. They can consume it in certain foods (fish liver oil and, to a lesser extent, egg yolk are good sources). Alternatively, skin cells have the ability to synthesize it from a cholesterol-like precursor. However, this process requires the energy of UV radiation. Theoretical research on the dose of ultraviolet radiation required to produce vitamin D3 suggests that for moderately to darkly pigmented individuals:? There is enough sunlight reaching the tropics to meet a human's entire requirement for vitamin D3 throughout all months of the year. This is indicated by the dotted area on the map.? In the area indicated by narrowly-spaced obliques, there is not enough ultraviolet light to synthesize vitamin D3 in human skin for at least 1 month of the year. In the area indicated by widely-spaced obliques, there is not enough UV light for the skin to synthesize vitamin D3 in any month of the year. Fig.4: amount of UV light available to synthesize recommended levels of vitamin D for a moderately to darkly pigmented person at various locations around the world Skin Whitening Skin whitening is the practice of using substances, mixtures or physical treatments to lighten skin colour. Skin whitening treatment works by reducing the content of melanin of the skin. Many agents have been shown to www.ujpsr.com be effective in skin whitening; some with beneficial side effects like antioxidants which can reduce the risk of cancer of certain types [9]. As discussed earlier, melanin is synthesized in melanosomes produced in melanocytes. 45
The synthesis of melanin involves a chain of enzyme catalyzed chemical reaction and non-enzyme catalyzed reactions. The main precursor of melanin is L-tyrosine. The first step is the conversion of L-tyrosine to L-DOPA; this is the rate limiting step catalyzed by enzyme tyrosinase. Tyrosinase activity is very important. If uncontrolled during melanoma, it results in increased melanin synthesis. Decreasing tyrosinase activity has been targeted for betterment or prevention of the conditions related to hyperpigmentation of the skin such as melasema and age spots. Several polyphenols, including flavonoids, substrate analouges, free radical scavengers copper chelators, have been known to inhibit tyrosinase. Henceforth, the medical and cosmetic industries are focusing research on tyrosinase inhibitors to treat skin disorders [10]. To accomplish the reduction of melanin concentration in the skin there are several possible mechanism of actions: Inhibition of tyrosinase: The catalytic action of tyrosinase is inhibited (slowed or nearly stopped) by the skin whitening agent. Inhibition of the expression or activation of tyrosinase: The antimelanogenic agent causes that less tyrosinase is generated or that tyrosinase is not activated to its functional form. Some of the skin whitening agents are: Hydroquinone, tretinoin, arbutin, kojic acid, azelaic acid, vitamin C, glutathione, alpha hydroxyl acids, niacinamide, CONCLUSION Scavenging of the intermediate products of melanin synthesis. Preventing the transfer of melanosomes to keratinocytes. Directly destroying existing melanin. Destroying melanocytes. monobenzone, mequinol, mercury, ellagic acid, ferulic acid, etc. Human skin pigmentation is based on the type of UV radiation that is rich in a particular geographical area. Say for the lands near to equator, due to high incidence of UV- A radiation there is breakdown of folate in the deeper tissues of the body. Folate is responsible for the synthesis of DNA. Thus, if folate deficiency occurs there may be mutation in the DNA leading to cancer. To avoid this there is the production of eumelanin in high amounts in the skin REFERENCES 1. en.m.wikipedia.org/wiki/melanin?_e_pi_=7%2 CPAGE_ID10%2C401250994 2. Gregory S. Barsh et.al, PLoS Biology http:// biology.plosjournals.org, Volume 1, Issue 3, Page 019-022 3. Meredith P, Riesez J (February 2004). "Radioactive relaxation quantum yields for scientific eumelanin" phytochemistry and phytobiology. 79(2):211-6 4. www.wikipathways.org/index.php/pathway: WP377 5. www.pinterest.com/pin/18556244712202547/?_e_pi_=7%2cpage_id10%2c5944004426 leading to darker pigmentation and higher reflectance of light. The land towards the poles have greater incidence of UV-B radiation which cannot penetrate into the deeper tissues of the skin and no destruction of folate occurs. But, there is the requirement of vitamin D3 whose synthesis in the body requires UVB photons and thus resulting in the production of pheomelanin giving a depigmented skin and higher absorbance of light 6. http://sciencecases.lib.buffalo.edu/cs/files/skin_ pigmentation.pdf. 7. Journals.plos.org/plosbiology/article/figures? id=10.1317/journal.pbio.0000027 8. http://www.pnas.org/content/107/supplement_2 /8962.full 9. en.m.wikipedia.org/wiki/skin_whitening?_e _pi_=7%2cpage_id10%2cpage_id10%2c 8269145701 10. en.m.wikipedia.org/wiki/tyrosinase?_e_pi_ =7%2CPAGE_ID10%2CPAGE_ID10%2C492 707666 www.ujpsr.com 46