Thursday, June 27, 2013

What is pigmentation?


Structure and Functions

One of the most apparent human characteristics is the color of a person’s skin. Five pigments play major roles: melanin, melanoid, carotene, hemoglobin, and oxyhemoglobin. Melanin occurs in the greatest variation and is the most important of the five; in large amounts, it can mask the effects of the other pigments.



Melanocytes are cells that convert tyrosine, an amino acid, into the black pigment called "melanin." The rate of production is controlled by a hormone called "melanocyte-stimulating hormone (MSH)," which is released by the anterior pituitary gland. About a thousand melanocytes occur on each square millimeter of the body (with the exception of the head and the forearms, which have twice as many). Interestingly, all human races vary greatly in color but tend to have the same number of melanocytes, which inherit different abilities to make melanin.


When humans are compared, an uninterrupted array of shades of skin color is found. Traits that show such continuous variation are thought to be controlled by several sets of genes (polygenetic inheritance). Thus, several sets of genes were believed to control the amount of pigmentation. In 2005, researchers at Pennsylvania State University found two variant expressions of a single gene that may be responsible for the observed distribution of human skin color.


Melanocytes convert tyrosine into
melanin by several chemical steps that involve the key enzyme tyrosinase. A functional tyrosinase molecule consists of different amino acids (the building blocks of proteins) and copper. Traces of copper are in the normal human diet and provide the amounts needed for the enzymes.


Tyrosine, the molecule that is converted to melanin, is one of twenty amino acids occurring in biological systems that chain together in various ways to make up different proteins. Eight of these amino acids are essential—that is, they must be present in the diet. The remaining twelve amino acids can be made by chemical modification of the others. Tyrosine is not an essential amino acid. Ample amounts of tyrosine occur in all meats and in most dairy products. If it is not taken into the body in sufficient amounts, however, it will be made from other amino acids. Either way, tyrosine is delivered to the melanocytes and changed into melanin. This product, with its high molecular weight, functions to protect the skin from excessive ultraviolet (UV) radiation.


UV radiation is an invisible part of the sun’s radiation having wavelengths from one hundred to four hundred nanometers. Humans can see the colors of the spectrum from red through violet. Wavelengths of radiation that are slightly longer than red (infrared) cannot be seen but are detected by the body as heat. Wavelengths that are shorter than violet, such as UV, cannot be seen or felt. Nevertheless, UV radiation penetrates the body. In moderation, UV light is valuable for humans because the body uses its energy to synthesize vitamin D. Vitamin D allows the intestinal absorption of calcium to be used for skeletal growth and for nerve and muscle function.


UV radiation poses several risks. A sunburn involves UV radiation damage to epidermal skin cells, which release chemicals that dilate blood vessels, causing redness. Swelling and blistering may occur. When large numbers of cells are destroyed, the skin speeds up production of new cells, which forces the burned cells to peel off. UV radiation also can change the skin’s collagen, a protein that holds tissues together in much the same way that concrete is reinforced by steel rods. The changes in the collagen, possibly by causing cross-linkage between fibers, can permanently wrinkle the skin. Finally, many researchers agree that UV light may also inhibit the immune response by damaging Langerhans cells in the epidermis. When damaged, these large cells lose their ability to alert the other cells of the immune system to infection. The most serious danger is that UV radiation may alter the genetic code within cells, causing cancer.


Melanin protects the cells of the body by blocking and absorbing UV light. People who have more melanin by heredity are not at as high a risk as those who are lighter. (This is not to say that dark-skinned people should not protect themselves from the sun.) In all cases, exposure to UV radiation immediately causes the skin to darken by causing oxygen to combine with the melanin that is already present. Exposure also increases the rate of melanin production and speeds its distribution to other cells, producing more darkening.


Melanocytes are found at the bottom of the outer layer of the skin, which is called the "epidermis." They are also at the base of the shafts of hairs and in the eye, producing coloration of the iris and in the black membrane of the eye behind the retina. The pigment-producing melanocytes in the skin are found at the base of the epidermis among cube-shaped skin cells that cannot make pigment. About thirty-six of these epidermal cells occur for each melanocyte. Melanocytes have long extensions that reach out to protect the regular skin cells. Furthermore, melanin can also be transferred to epidermal cells. Skin color is also influenced by the distribution and size of the pigment granules in the melanocytes. Very dark skin tends to have single, large granules. Lighter skin tends to have clusters of two to four smaller granules.


On a larger scale, small uneven clusters of pigment are called "freckles." These spots of melanin show mostly in lighter-skinned people, are controlled by heredity, and appear with sun exposure to the skin. Because of this uneven distribution of melanin, other cells among the freckles are not protected and can easily be sunburned.


Moles (nevi) are larger, dark spots of melanin that tend to increase as a person ages. Two types occur: the pigment can be deposited into the dermis (intradermal nevi) or can be found between the dermis and the epidermis (junctional nevi). The first type of mole tends to be elevated and have hair growing from it. The second tends to be flat and very dark.


Large amounts of melanin in
hair will cause it to be black. Lesser amounts make it brown, and still less causes it to be blond. White or gray hair has no melanin. Yet a separate gene for a reddish, iron-containing pigment can be inherited. If two of these recessive genes are present, then the hair will be red. Depending on the amount of melanin that is also present, such people range from almost purely red hair to a strawberry blond color to a reddish-brown (auburn). Larger amounts of melanin will cover the red pigment completely.


Lack of melanin in the iris of the eye will scatter light and cause the eye to reflect blue. Larger amounts cause the eye color to be darker. The pigment in the iris serves to block radiation that could sunburn the retina. In 1992, investigators at Boston College found that eye sensitivity increases when the amount of melanin is greater.


Melanin breaks down as it moves toward the outer layers of the epidermis, forming a chemical called "melanoid" in the process. Melanoid can be seen as a yellow color in the thick (calloused) skin of the palms of the hands and the soles of feet.


Carotene is a yellow-to-orange pigment that tends to accumulate in the layer of fat under the skin. This pigment is also responsible for the color of carrots, yellow vegetables, and the yellows in autumn leaves. When taken into the body, carotene is stored in the liver and converted into vitamin A, which is used in vision. Females usually store more carotene than males because of their higher percentages of fat. Asian peoples tend to have combinations of low melanin and higher carotene that produce a yellowish skin hue.


Hemoglobin and oxyhemoglobin are pigments that are found inside red blood cells. Hemoglobin is dark red but looks bluish through the skin. If hemoglobin combines with oxygen, it is called "oxyhemoglobin." Oxyhemoglobin is bright red. Skin color from this pigment varies with the amount of blood that is circulated at the surface of the dermis, the relative amounts of hemoglobin and oxyhemoglobin that are present, and the densities of other pigments. Hemoglobin and oxyhemoglobin affect the color of light-skinned people more than of darker people. The skin of lighter people generally looks reddish, with oxygen-poor veins appearing blue.


Rapid change of hair color, from dark pigmented to gray or white, is impossible because of the slow growth rate of hair. Melanin is deposited into the hair shaft at the root. The hairs grow outward at a rate of about thirteen millimeters a month. Hence, a loss of pigment production would take a long time to show. The myth of rapid change may be based on diseases that cause all the pigmented hair to fall out overnight, leaving only white hairs.




Disorders and Diseases

Pigmentation can be abnormal and associated with disease. Excess
adrenocorticotropic hormone (ACTH) can increase melanin. ACTH contains several hormones, including MSH. Addison disease involves the overproduction of ACTH. Also, certain injuries such as burns, chemical irritations, or some infections may cause an increase in pigmentation, as can pregnancy. Injuries in which melanocytes are destroyed may result in scar tissue that lacks pigmentation. An excessive intake of carotene can cause light skin to turn orange, a condition called "carotenemia."


Skin cancer
has increased over time. In the late twentieth century, the rate doubled every decade from the 1960s to the 1990s. The
ozone layer, a thin layer of gas molecules consisting of three oxygen atoms, was being depleted by chemicals such as refrigerants that were released into the atmosphere. This layer protects life on the planet from the full shower of
ultraviolet radiation that comes from the sun. In 2013, according to the World Health Organization, some two to three million skin cancers were being diagnosed annually. Any changes in the skin, such as a mole that changes in color or begins to grow, should be shown to a doctor. Although moles and other abnormalities in pigmentation are not usually dangerous, some may develop into melanomas.


Researchers have been trying to discover if it is possible to tan safely. Attempts have been made to develop better creams to block UV radiation. Skin cancer is less common among dark-skinned people; it has been reasoned that if melanin could be put into a skin cream, lighter-skinned people could have more of this natural protection. Unfortunately, many sources of melanin are expensive.


Presently, the best way to avoid skin cancer is to avoid the sunlight, especially when and where the light is most intense—at midday, near the equator, during the summer at other latitudes, at high altitudes, and in highly reflective environments such as sand or snow. Additional protection can be found by using a sunscreen lotion with a high sun-protection factor (SPF) of at least 15. SPF 15 permits fifteen times longer exposure before burning (compared to using no sunscreen), and SPF 30 is thought to protect even the fairest skins. The American Academy of Dermatology recommends using SPF 30 or higher.


Nevertheless, even with frequent applications of sunscreens, people may be putting themselves at risk of melanoma, the most serious skin cancer. Specifically, deoxyribonucleic acid (DNA) absorbs and can be directly damaged by the 280 and 315 nanometer range of UV radiation, and it was formerly assumed that this range, called UVB, was the only one about which people had to worry. Sunscreens were initially developed to block only UVB, the “burning rays.” Data collected by Richard B. Setlow and his colleagues at Brookhaven National Laboratory in 1993, however, indicated that longer wavelengths, including some visible light and UVA (315–400 nanometers), can also damage DNA. Setlow suggested that melanin itself absorbs this energy, setting off chemical reactions that produce chemicals that then damage the melanocytes. This process may be the cause of melanoma. The current consensus is that people should protect themselves from all sunlight, using a broad-spectrum sunscreen lotion that protects against both UVA and UVB. The same risks apply to tanning salons.


Most melanomas are skin cancers. They can also be found inside the eye, as a black spot on the white of the eye, on the iris, or in the center of the field of vision. Treatment of such growths with radiation or surgical removal of the tumor are options. Removal of the entire eye may be necessary. Preventive measures include sunglasses that filter UV light. According to the American Academy of Ophthalmology, sunglasses should block 99 to 100 percent of UV radiation. Most manufacturers label their sunglasses.


In 1991, a controlled study was done in which injections of synthetic MSH were tested. The goal was to help prevent sunburn and skin cancer in high-risk individuals who tan poorly. Those receiving MSH showed significant tanning compared to those who received injections of a placebo. Some mild side effects occurred in the MSH group, including some brief flushing and vague stomach discomfort after the injection.


There are several irregularities of pigmentation. If the tyrosinase enzyme is missing, a person will produce no melanin. This condition is inherited among all races, and such a person is called an "albino" (Greek for “white”). Actually, the lack of melanin allows hemoglobin to determine the skin color. In some types of albinism, an affected individual produces reduced amounts of melanin, resulting in an appearance that is only slightly lighter than that found in the individual's family and ethnic community. All albinos have less protection from the sun and, in addition to the risks to the skin, have poor vision because of light reflections off the back of the eye that normally would be absorbed by pigment. With no pigment in the iris, they are also more likely to suffer damage to their retinal cells, resulting in blindness.


Especially in lighter-skinned people, a lack of hemoglobin (anemia) will cause paleness. If a person’s body circulates more blood into the dermis, the skin will appear more reddish or flushed. This could signal that the body is attempting to cool itself or that a person is embarrassed. If the body is cold or emotionally shocked, it may reduce circulation of blood to the surface of the dermis and the individual will appear pale. Lack of normal sunlight can cause a person to slow the production of melanin. A person who is exercising by swimming in cold water may not circulate blood as quickly as it is needed, and the increase of hemoglobin may turn that person blue, a tone that is noticeable in people with both large and small amounts of melanin.




Perspective and Prospects

Scientists believe that the first humans probably had their origin in Africa and were darkly pigmented. As people migrated to the higher latitudes, where the radiation from the sun was less direct, having less pigment may have been adaptive. Less melanin would allow these people to synthesize needed vitamin D where there was less direct sunlight and less UV light. Before individuals began to migrate over long distances, populations were neatly distributed with darker skins near the equator and lighter skins in northern Europe. Inuits are an interesting exception: they have dark skin and live in a northern latitude. Their diet, however, has traditionally included fish livers with sufficient vitamin D.


The possibility of danger from the sun and other radiation is only a recent discovery. Ultraviolet radiation was discovered in 1801. By 1927, H. J. Muller showed in the laboratory that x-rays cause changes in the genetic code of fruit flies that can be inherited. Such changes, called "mutations," can be harmful. Further investigations showed that UV light, while not as dangerous as x-rays, can also cause mutations. The likelihood of mutation in an organism is proportional to the dose of radiation that is received; spacing out the exposure makes no difference.


Attempts to classify races by description of skin color have given little return. Paul Broca (1824–80) developed an elaborate table of twenty colors for cross-matching with the eyes and twenty-four colors for cross-matching with the skin. The color of the skin, however, is extremely difficult to judge: the color itself changes with environmental and physiological conditions, the ability of observers varies, and the lighting conditions under which comparisons are made can make a difference in the results.


To avoid some of these problems, studies have been performed with a device that measures the reflection of various wavelengths by the skin. In 1992, a study of members of the Jirel population in Nepal showed that the reflections from measurements of upper arm skin using three different wavelengths varied as if the reflective properties were controlled by only a single set of genes. Evidently, the use of various wavelengths gives little additional information about color differences.




Bibliography


A.D.A.M. Medical Encyclopedia. "Skin - Abnormally Dark or Light." MedlinePlus, May 13, 2011.



"Albinism." Mayo Foundation for Medical Education and Research, April 2, 2011.



Balter, Michael. "Zebrafish Researchers Hook Gene for Human Skin Color." Science 310, no. 5755 (December 16, 2005): 1754–55.



Freinkel, Ruth K., and David T. Woodley, eds. Biology of the Skin. New York: Parthenon, 2001.



Greeley, Alexandra. “Dodging the Rays.” FDA Consumer 27 (July/August, 1993): 30–33.



Greener, Mark. “Gene for Red Hair Could Shed Light on Skin Pigmentation.” Dermatology Times 20, no. 12 (December, 1999): 19.



Guttman, Cheryl. “Pigmentation Disorders Common in Asians.” Dermatology Times 20, no. 8 (August, 1999): 24.



"Health Effects of UV Radiation." World Health Organization, 2013.



Levine, Norman, ed. Pigmentation and Pigmentary Disorders. Boca Raton, Fla.: CRC Press, 1993.



Schalock, Peter C., ed. "Overview of Skin Pigment." Merck Manual of Home Health Handbook, January, 2013.



Turkington, Carol, and Jeffrey S. Dover. The Encyclopedia of Skin and Skin Disorders. 3d ed. New York: Facts On File, 2007.



"UV Radiation." United States Environmental Protection Agency, June, 2010.



Weedon, David. Skin Pathology. 3d ed. New York: Churchill Livingstone/Elsevier, 2010.

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