Volume 14 | Issue 1 Article 2

1952 Melanin Pigmentation In Animals Donald Blaney Iowa State College

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Recommended Citation Blaney, Donald (1952) "Melanin Pigmentation In Animals," Iowa State University Veterinarian: Vol. 14 : Iss. 1 , Article 2. Available at: https://lib.dr.iastate.edu/iowastate_veterinarian/vol14/iss1/2

This Article is brought to you for free and open access by the Journals at Iowa State University Digital Repository. It has been accepted for inclusion in Iowa State University Veterinarian by an authorized editor of Iowa State University Digital Repository. For more information, please contact [email protected]. Melanin Pigmentation In Animals

Donald Blaney*

THE CAUSES of coloration in animals ample) frequently serve some other, more is a problem that has occupied man's important function while their color is mind for centuries. That such is the case merely incidental. Of all pigments, only is certainly the result of the complexity melanin persists in a histological prepar­ of the problem, for it is not one which is ation. Any others, if present, are de­ easily solved and relegated to a place of stroyed. minor importance. The color which we Because of the above facts-the wide perceive is the net result of a myriad of distribution of melanin and its dominant inter-actions and contributing elements. role in determining coloration - this pig­ Nervous control, hormones, environ­ ment alone will be treated extensively in mental conditions such as temperature, the folowing pages. In order to discuss light, and the color of the surrounding are melanin with some degree of complete­ but a few of the known factors affecting ness, it was found convenient to divide the animal coloration. Perhaps the number of material into four topics. The first is con­ unknown factors far outweight these. cerned with the chemical reactions which The pigmentation problem, however, is lead to the synthesis of melanin and the not insurmountable, nor totaly devoid of various factors which affect its formation unity. In fact, all present evidence points as far as these are known. This is followed to the existence of but one type of pig­ by a section devoted to the discussion of ment-forming cell in the integument of the structural units or specialized pig­ fish, birds, man, and other vertebrates. ment cells in the organism, their des­ This cell manufactures a substance known cription, origin, and distribution. The as melanin and is called, therefore a third section is concerned with those melanoblast. To propose that this cell animals that can change their color in re­ alone is responsible for the extremely di­ sponse to the environment. While only a verse coloration in various species or rather small percentage of the animal within a single species would seem to me kingdom seems to possess this ability, it presumptuous. It is probable, however, is not impossible that a study of this that this is not only the most important phenomenon may lead to a better under­ source of pigment in most species but also standing of pigmentation in more typical the only pigment cell common to so wide animals. The last section is devoted to ab­ a variety of animals. It is true that pig­ normalities in the production and distri­ ments of other types occur in blood, the bution of coloring matter in animals. retina, the liver and other organs; but Chemical Formation of Melanin these pigments (hemoglobin, for ex- It is now an established fact that mel­ anin can be formed from the amino acid * Mr. Blaney is a graduate student in biological tyrosine, and most investigators agree chemistry and wrote this paper for a course in graduate veterinary physiology. that the ultimate source of cutaneous pig-

14 Iowa State College Veterinarian mentation in man and probably most of the surrounding cells. The melanoblast is the lower animals is this amino acid. The fragile and often spongy. The nuclei vary original work that eventually led to these greatly in shape. They may be oval, conclusions was begun in 1895 by Bour­ spherical, notched, kidney-shaped, even quelot and Bertrand (6). They recognized double. The center of the melanoblast fre­ that a substance present in Russula nigri­ quently contains "premelanin" granules. cans was turned black by an enzyme in These are not darkly colored but become the same fungus. The substance was so by means of the dopa staining tech­ identified as tyrosine and the enzyme nique. It is only in the processes that was given the name tyrosinase. It has melanotic maturation is complete. The since been found widely distributed in granules, then, migrate from the center of the vegetable kingdom and is present in the cell to the branches. From these many invertebrates. Recently there has branches the pigment is distributed to the been indirect evidence of tyrosinase in other cell of importance in pigmentation, the vertebrates (9). The characteristic the melanophore. These are simply cells property of the enzyme is that in the pres­ which, being in contact with the processes ence of air it changes tyrosine solutions to of the melanoblasts, have picked up the red, reddish brown, and finally black. An pigment and store it. This transfer has insoluble pigment, melanin, is deposited. actually been observed in the case of pig­ Since the early work by Bourquelot and mentation of the malpighian or germinal Bertrand (6) many theories have been layer of the epidermis. Transfer to dermal proposed regarding the action of tyro­ melanophores, which also exist, has not sinase on the amino acid. These theories been demonstrated, and, in fact, how this are composed of many chemical reactions transfer is effected through the basal involving such things as pH and ultra­ membrane is unknown. voliet light. From the foregoing discussion we may The melanin production picture is yet conclude that the melanoblast is a type of more complicated by the fact that injec­ glandular cell. It elaborates and excretes tion of sex hormones may increase mel­ its product. However, the product is a anogenisis (10). Contrariwise, vitamin C, solid and insoluble. Furthermore, it is ex­ ascorbic acid, inhibits pigmentation of creted neither directly externally nor into normal animal tissues when fed in excess vessels, but rather into other cells. Be­ (18). About all that is certain is that cause of this unique situation, Masson tyrosine is the precursor of melanin pig­ suggests the cells be called "cytocrines" in ment. preference to endocrines or exocrines (14). The Melanin-containing Cells As was stated previously it was at one It was formerly believed that any cell time believed that cells containing pig­ which contained pigment had produced ment produced it. To most investigators it. Now it is well established that there pigment seemed to appear in various parts are two cell types associated with cutan­ of organisms without giving evidence of eous pigmentation. One produces melanin, the place of origin. In 1934 and succeed­ these are called melanoblasts. The other ing years experimental proof was pre­ contains but cannot manufacture it. These sented to the effect that pigment cells, are the melanophores or chromatophores the melanoblasts, arise from the neural (14). crest in amphibia, birds, and in the mouse A typical melanoblast resembles other (7,17). Such an origin makes readily cells in several respects. It is provided understandable the distribution of mela­ with a cytoplasm enclosing a nucleus. The nin pigment. It is found in many struc­ cell body is angular, and extending from tures of ectodermal origin such as the the vertices of the angles are minute, epidermis and hair, mucosal membrane, threadlike branches. It is by means of sensory organs, and so forth. There re­ these dendritic processes that the mela­ mains, however, some question as to the noblasts come into intimate contact with neural crest origin in man and in fact

Issue 1, 1952 15 many vertebrates. Indeed, the distribu­ since there are few if any dendritic tion of the pigment does vary somewhat processes that pass down from the mela­ in man and the lower vertebrates and noblasts. The pigment is transferred to invertebrates. In the lower forms the pig­ reticulo-endothelial cells and eventually ment occurs in the deeper parts of the to the lymphatic nodes. It is doubtlessly body as well as in the skin. Weidenreich gradually destroyed during the transit, has pointed out that pigment "layers" for no increasing accumulation of it can be noticed in many animal types (20). occurs normally in any part of the or­ These are 1) a cutaneous layer which ganism. may be subdivided into dermal and epi­ There has been no demonstration of a dermal; 2) a perineural layer around the relation between melanoblast activity and central nervous system; 3) a pericoelomic the nervous system, except in the case of layer around the peritoneum; 4) a peri­ those animals that possess the ability to vascular layer about the blood vessels. change their color rapidly. These will be In cyclostomes, fishes, amphibia, and rep­ treated briefly in the next section. tiles, all of these layers may be present. Color Changes In Animals In birds and mammals, deeper pigment layers are usually lacking or occur at best While the ability to change color in reo as "vestiges." sponse to environment is an attribute that Some general statements can be made is not universally distributed throughout about the pigmentation in the cutaneous the animal kingdom, it is found in a layer. As a rule, the pigment is more goodly number of species. Cephalopods, abundant in darker skins, but the paral­ crustaceans, fishes, amphibians, and liz­ lelism does not always hold true. The ards have well developed pigmentary darker or lighter shades of the pigment effector systems. Some investigators feel itself, the depth of location in the skin, that facial blushing in humans is a vestige and the colloidal or granular nature of of a similar system. the melanin particles contribute greatly When one begins to consider color in determining the hue of the skin. Mela­ change in animals, he generally thinks nin is seen mostly in the deep areas of first of the chameleon. The common frog, malpighian or germinal layer, always in however, can exhibit a similar, but the basal layer of cells, often in upper slower, color response. If placed in a layers. Small amounts are normally found centimeter of water in a cool dark room as high as the stratum corneum, larger and on a dark surface, a frog becomes amounts after exposure to radiation. The intensely black in two days. In a dry melanoblast itself is always found con­ vessel in a warm, brightly illuminated nected to the basal membrane. Dendritic room, the same frog will assume a chrome processes connect various melanoblasts or lemon color in two days. Brown, green, with one another and project upward and other intermediate colors are seen in through the basal cell layer to the higher other situations (11). layers which in turn receive melanin from How all this comes about has been them. In areas of lighter pigmentation, explained to a certain extent as follows. the eyelids and palms for example, mela­ In the integument of the animal exists noblasts are less common but not absent. a great number of pigment-bearing cells Melanin pigment is also present in the which are capable of altering their shape. corium. It is found only in superficial When the animal is neither very dark nor mesenchymal cells, usually in small light, the cells are of an irregular star­ amounts. It is quite regularly proportion­ like or stellate configuration. When the ate to the intensity of the neighboring animal is pale, the pigment granules epidermal pigmentation and is often lack­ within the cell are concentrated in min­ ing in the paler cutaneous regions. It is ute aggregations, so that they tend to accepted by all that this pigment arises assume a small spherical contour. In the from the epidermal melanoblasts. How it dark skin situation, the pigment is found crosses the basal membrane is unknown (Continued on page 46)

16 Iowa State College Veterinarian Melanin- nerves were cut, the chromatophores of (Continued from page 16) the regions supplied by these nerves took on an intermediate tint and remained in diffusely spread throughout processes this state (15). Later the actual location which almost appear to interlace with in the brain or the controlling center was those of adjacent pigment cells forming a determined. In fish thus far tested the continuous network of black coloring color change depends upon the eye. matter. Blinded fish show no response to the color Expansion and contraction of black of the environment. The possibility of melanin cells could produce only hues of double innervation of chromatophores, black and various greys on a white back­ that is, by the sympathetics and para­ ground. Of course this alone would be sympathetics, has neither been confirmed inadequate to explain the array of colors nor disproven. that are at the disposal of the chameleon In frogs the color response is princi­ and the frog. There must exist other pig­ pally under hormonal control. Hogben ments in addition to the dark melanin, completely removed the pituitary gland and granules that have a red or yellow from a number of amphibians, and the color have been noticed. Whether these animals were left in a permanently pale pigments are entirely unrelated to mela­ condition (11). Examination of the skin nin, or whether they merely represent showed that the melanophores were in a stage in the oxidation of precursors to maximum contraction. The injection of melanin or in the physical nature of the pituitary extract into these animals re­ particles is a question that has not been sulted in a temporary darkening due to settled. At present, evidence favors the the expansion of the melanophores. Nerve latter viewpoint. At any rate, several cutting experiments in the case of am­ such color systems of different tints prob­ phibia have largely yielded negative re­ ably exist side by side in the integument sults. of the animal. Through alternate degrees As was mentioned in the preceding of expansion and contraction of the vari­ section, no relation has been established ous systems, it is conceivable that a wide between the nervous system and the variety of colors could be produced. melanophores or melonoblasts in the One immediately wonders how such a higher vetebrates. Hormones, however, complicated system is controlled. Other play some unknown role in the formation effectors such as the muscles and glands of melanin. During pregnancy, when there have been shown to be under the control is an increase in hormonal circulation, an of nerves or hormones, and we might abnormal production of melanin, even to expect a similar control for the pigmen­ the extent of tumor formation, may occur. tary effector system. It turns out that Additional malfunctions of the pigmen­ either, or both, the nerves and the hor­ tary system are discussed in the next mones are involved in color response, section. depending on the animal in question. In the cephalopods the chromophore has Abnormalities neumerous radiating smooth-muscle fibres As is the case with most systems in provided with nerves. The muscle fibres any organism, a variety of abnormalities are attached at one end to the elastic occur in the method of pigment produc­ envelope of the cell and at the other to tion. These may be as insignificant as an some point in the adjacent tissue. When absence of pigment in a small area where the nerves initiate a contraction of the it is naturally expected or as dangerous muscle fibre the chromatophore is drawn as a melanotic tumor, some of which into a thin, flat disk and the skin appears are as malignant as any known cancerous dark. In fish, histological studies have growth. These abberations have been demonstrated that melanophores are most extensively studied in man, but under direct nerve control (2). Pouchet there is litle reason to doubt that similar has shown, in addition, that when certain (Continued on page 56)

46 Iowa State College Veterinarian Melanin- if the vitiligo has existed for only a short (Continued from page 46) time. If several years have elapsed, the disorders occur in the lower forms. pigment cannot be restored. The malfunc­ Melanotic tumors may be benign or tion is again attributed to the disappear­ malignant. The simple benign type are ance of some enzyme in the tyrosine re­ commonly known as moles or nevi. They action. are particularly common in the white The effects of lentigo are the reverse of race, the average man having about the above. An area, usually quite small, twenty. The nevi result from an over­ becomes hyperpigmented due to an in­ active melanoblast and are potentially ternal unknown stimulus of the mela­ subject to continued development to the noblasts. In simple lentigo, this situation state of a malignant melanoma. No sta­ is harmless since the pigmented cells tistical data seems to be available as to make their way to the upper layers of how often this occurs, but it is certainly the skin and are sloughed off. The condi­ infrequently since melanomas constitute tion at this stage is in no way malignant, only about one percent of all cancerous but it need not remain so. A disorder growths. Nevi on the feet and genitals are known as lentigo maligna seems to be a more likely to undergo malignant de­ derivative of lentigo. Melanoblasts in­ generation than a similar tumor in other crease rapidly and migrate into the upper parts of the body. The transformation fre­ skin layers and also into the dermis. quently occurs with approaching puberty, From the dermis they are cast off and and the opinion now exists that it is metastasis occurs. Tumors begin in near closely related to the endocrine system, and distant parts of the body. notably the gonads and the suprarenal Melanosis is a term used to define the cortex. Malignant melanotic tumors may case in which an organ is perfectly nor­ also appear during pregnancy. These are mal in every respect except that it is of a type of particularly rapid growth and covered with, or contains, considerable are almost always fatal. In general, it amounts of melanin pigment. It occurs may be said that fair or blond individuals quite frequently in calves, usually in the are found more often to develop malig­ form of black spots in the subcutaneous, nant melanomas; in Negroes the incidence subperitoneal, or intermuscular connec­ is very low. tive tissue. It seems to disappear in later There is one well-known abnormality life as it is very rare in adult cattle. in man and other animals that is char­ Generalized melanosis, in which practi­ acterized by the name albinism. In total cally all of the internal organs are darkly albinism no melanin is produced due most pigmented has been noted in a male tur­ probably to a lack of some enzyme (s) in key and a domestic pig. External mela­ the transformation of tyrosine to the pig­ nosis occurs occasionally in humans, and ment. The hue of the skin, eyes, and other sometimes half of the body is black or parts of the organism is principally a re­ dark blue. The individual is otherwise flection of the red blood pigment, hemo­ healthy. globin. Partial albinism may also occur. The most recent report of abnormal The lack of pigment in the skin and hair pigmentation concerns a hyperpigmenta­ is limited to certain areas only. The eyes tion that developed during treatment of are usually pigmented. leukemia patients (21). Ten patients were Another deviation from normal pig­ given daily dosages of folic acid antago­ mentation is called vitiligo. It is a case, nists, and in seven of these, abnormal like partial albinism, in which certain darkening of the skin occurred. Almost areas of the skin or hair lack pigment. the entire body surface of one patient, It differs from albinism in that the af­ who was kept alive nine months by the fected area is usually more restricted and treatment, was dark brown before death. was at one time pigmented. Melanino­ Examination of skin sections by the genesis can be initiated again in these "dopaoxidase" activity method indicated areas by treatment with ultraviolet light true melanogenesis.

56 Iowa State ColLege Veterinarian References Observations on the estrous cycle of 30 1. Arnow, J. Bio!. Chem., 168, 433 (1947). mares from January, 1944, to June 1946, 2. Ballowitz, Zeit. wiss. Zoo!., 56, 1893. revealed that the estrous cycle in these 3. Becker, Am. J. Cancer., 22, 17 (1934) 4. Block, Am. J. Med. Sci., 177, 609 (1929). mares was not seasonal but that it contin­ 5. Blum, Phys. Rev., 25, 498 (1945). ued thoughout the year in the majority of 6. Bourquelot and Bertrand, Compt. rend. Soc. the mares observed. However, there was Bio!., 67, 582 (1895). 7. DuShane, Science, 80, 620 (1934). a noteworthy decline in the percentage of 8. DuShane, Rev. Bio!., 18, 109 (1943). mares that showed estrum inApril and 9. Figge, J. Exp. Zoo!., 78, 471 (1938). 10. Hamilton, Proc. Soc. Exper. Bio!. and Med., May. The cycles were irregular and varied oW, 502 (1939). in length from six to 113 days. The irregu­ 11. Hogben, "The Pigmentary Effector Systems." larities were most pronounced during the 12. Masson, J. Bio!. Chem., 168, 433 (1947). 13. Masson, ibid., 172, 83 (1948). months of February to April. The average 14. Masson, "The Biology of Melanomas," p. 19. length of the estrous cycle for the whole 15. Pouchet, Jour. Anat. Physio!., 8, 71. year was 29.9 days. 16. Raper and Wormall, Biochem. J., 19, 84(1925). 17. Rawles, Proc. Nat. Acad. Sci., 26, 673 (1935). Today somewhere between 40,000 and 18. Schroeder, Klin. W schr., 11, 553 (1932). 19. Szent-Gyorgyie, Dtsch. med. Wschr., 852 four million Americans have undulant (1932) . fever, or brucellosis. Masquarading under 20. Weidenreich, Z. Morpho!. and Anthropo!., 2, the symptoms common to many other di­ 59 (1912). 21. Waisman, Richmond, and Zimmerman, Proc. seases, undulant fever appears sometimes Soc. Expt!. Bio!. and Med., 75, 332 (1950). to be anything from psychoneurosis to 22. Zeissler and Becker, Arch. Derm. and Syph., 33, 109 (1936). scarlet fever. No two cases act exactly alike. Thousands of cases go undetected, diagnosed as peptic ulcers, arthritis, or In Colonial Days the church door even typhoid. Brucellosis germs will served as bulletin board to advertise dogs cause infection in practically any part of for sale. the body.

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