One of the fundamental pigment patterns seen among most vertebrate species including mammals is one wherein the back is darkly colored while the belly is whitish. Generally speaking, dark pigmentation among vertebrate species is brought about by the action of melanocyte- stimulating hormone (MSH) produced by and released from the intermediate lobe of the pituitary gland. This hormone stimulates the expression of melanin-containing pigment cells (melanophores, -cytes) and inhibits the whitish pigment cells (iridophores) on the back. It has been shown recently that the white belly pattern of frogs is partly due to the absence of melanin pigment in the belly skin because melanophores in this region are inhibited by the localized presence of a melanization inhibiting factor (MIF) present in belly skin. This MIF from frogs inhibits melanization of mouse melanoma cells in cell culture and a similar acting MIF from the pale belly skin of a pigmented mouse inhibits melanization of frog melanophores. This lends credence to the concept that an MIF or a family of MIF molecules is responsible for normal pigment pattern formation among all vertebrates. The proposed investigation is directed toward understanding the interaction between MSH and the putative MIF in the establishment of vertebrate pigment patterns. Most of the work will study the effects of these protein molecules in pigment cell cultures. A third little known factor, serum melanization factor (SMF), will also be involved in these experiments. The interactions among all three will be assessed. The basic knowledge to be derived from this study will have practical implications beyond that of "knowledge for its own sake." For example, the localized elaboration of MIF molecules could explain the greying of hair or the blanching of skin as in human vitiligo. Possible implications of MIF in diagnosis and treatment of human malignant melanoma are also possible.
