The discovery of the human melanocyte.

Around 2200 bc the first written description of a human pigmentation disorder, most likely vitiligo, was recorded, and from that moment the history of research into human pigmentation can be traced. For the following 4000 yr, the origins of human skin colour remained an enigma that was to generate a multitude of misconceptions. Even after European physicians began to dissect and compare dark and light coloured skin to reveal its underlying anatomy, the origins of skin and hair pigmentation were a matter of frequently erroneous speculation. The true source of human pigmentation was only finally revealed with the discovery of the melanocyte in the 19th century. Once tyrosinase was identified to be the key enzyme in pigment formation, attention focused on elucidating the chemical structure of melanin, an enterprise that remains incomplete. The developmental origins of the melanocyte were described from 1940 to 1960, and the concept of the epidermal melanin unit was introduced together with a description of the ultrastructure of the melanosome and melanosome transfer. With these advances came the realization that different skin types exhibit distinct differences at the histological level that relate to varying amounts of eumelanin and pheomelanin produced by the melanocytes. The foundation established over the past 4000 yr is the basis for all current research into this fascinating cell type.

Regulation of yellow pigment formation in mice: a historical perspective.

Pigment synthesis by hair follicle melanocytes is modulated by a large number of environmental and genetic factors, many of which are discussed in this review. Eumelanic (non-yellow) pigment is produced by hair follicle melanocytes following the binding of alpha-melanocyte stimulating hormone to melanocortin receptor 1. Binding of this hormone to the melanocyte membrane is blocked by agouti signaling protein (ASP) which is encoded by the agouti locus and results in the synthesis of yellow pigment, instead of non-yellow (black/brown) pigment. The cyclical release of ASP by hair follicle cells results in a black/brown hair with a subapical yellow band. This is the wild-type coat color pattern of many mammals and is called agouti. Several dominant mutations at the agouti locus in mice, induced by retrotransposon-like intracisternal A particles, result in ectopic over-expression of ASP and animals with much higher proportions of all-yellow hairs. This abnormal presence of ASP in essentially all body cells results in the 'yellow agouti obese mouse syndrome.' The obesity has been associated with binding of ASP to melanocortin receptor 4 inactivating the latter. The syndrome also includes hyperinsulinemia, increased somatic growth, and increased susceptibility to hyperplasia and carcinogenesis. The physiologic and molecular bases for these syndrome components have not yet been elucidated. This historically orientated review is subdivided, where applicable, into pre- and post-1992 subsections to emphasize the impact of the cloning of the agouti and extension loci and their protein products on the identification of the molecular and physiological pathways modulating the manifold aspects of pheomelanogenesis.

Acropigmentación reticulada de Dohi / Reticulate acropigmentation of Dohi

La acropigmentación reticulada de Dohi es un proceso discrómico consistente en la presencia de máculas hiper e hipopigmentadas con un patrón reticular, localizadas en el dorso de las manos y los pies, de aparición fundamentalmente en pacientes japoneses. Presentamos el caso de una joven de 20 años, de padre japonés y madre española, con lesiones cutáneas compatibles con una acropigmentación reticulada de Dohi. Este cuadro es de herencia autosómica dominante, aunque se han descrito casos de herencia recesiva y otros esporádicos como el nuestro. El diagnóstico diferencial debe hacerse con otros procesos con pigmentación reticulada como la acropigmentación reticulada de Kitamura y la enfermedad de Dowling-Degos (AU)

Charles University and pigment cell research.

A short review on the pigment cell research at Charles University in Prague is presented.

Tradition of basic and applied pigment cell research in Marseilles.

Melanogenesis, thyroid hormones and catecholamines synthesis share the same amino acid, free L-tyrosine for melanogenesis and catecholamines synthesis, L-tyrosine residues for thyroid hormones synthesis. The author describes basic and applied research on Melanogenesis and thyroid hormones metabolism in Biochemistry laboratory, School of Medicine, Marseilles since his arrival in 1962. He gives a short review of his participation in these two areas during his career in Marseilles, Yaoundé and Boston.

Tradition of pigment cell research at Charles University in Prague.

A short review on the history of pigment cell research at Charles University (Ch.U.) in Prague is presented. The famous Czech physiologist and professor J.E. Purkyne started the pigment cell research at Ch.U. already in 1837. He discovered melanin granules in the cells of substantia nigra of the brain. Later, in 1858, a Czech professor of medicine at Ch.U., B. Eiselt, as the first, described melanogenuria in 3 patients with generalized melanoma. Also some German professors at Ch.U. contributed to the research of melanins and melanogenuria in the past, especially H. Waelsch (1932). After the World War II, a Czech professor of medical chemistry at Ch.U., A.F. Richter with his young assistant J. Duchon continued in the chemical exploration of melanins (1954) and J.D. with Z. Pechan, B. Matous and S. Pavel devoted their attention to melanogenuria in melanoma patients (1962-1980). In 1967 they identified 2 new metabolites in melanoma urine: 5-hydroxy-6-methoxy and 6-hydroxy-5-methoxy-indole-2-carboxylic acids. J. Duchon with J. Borovanský and P. Hach also studied morphology and chemical composition of different melanosomes (1972-1979) and brought the first evidence that melanosomes consist of several proteins (1972). In 1980's 4 groups devoted to the pigment cell research and originated from Ch.U. were formed. The groups of J.B., of B.M. and of J. Vachtenheim in Prague and the group of S.P. who moved to the Netherlands (Leiden). As for the clinical aspects of the pigment cell research, the s.c. Hermanský-Pudlák syndrome published in 1959 and the histopathological classification of malignant melanomas estimated by J. Trapl (1957), should be mentioned. Therefore it is not surprising that, as a result of the tradition of pigment cell research at Ch.U., the 3rd European Workshop on Melanin Pigmentation was held in Prague already in 1981 and that, in 1998 again, Ch.U. was entrusted with the arrangement of the 8th Meeting of the European Society for Pigment Cell Research at the occasion of the Ch.U. 650th anniversary.

Melanins: an old problem revisited or the usefulness of infrared spectroscopy.

This mini review remembers the implication, thirty nine years ago, of professor Wegmann in a fascinating adventure on the serendipitous study of melanin, after that a case of Dubin-Johnson's icterus had been submitted to him. To this investigation have been applied, one after the other and often simultaneously, for the first time, the diverse technologies of pathology, histochemistry, histoenzymology, biochemistry and infrared spectrography, having permitted to detect for the first time melanin in a human liver, associated with a melaninuria. But it was thanks to a marvellous collaboration with many colleagues that we came to a good end. It was the beginning of the interdisciplinary science of Cellular and Molecular Biology. To day remains to explain the mechanisms leading to the formation of melanin in liver and spleen.