Paracrine regulation of melanogenesis

Melanocytes are generally characterized by the basic ability of melanin synthesis and transfer to adjacent keratinocytes. This constitutes an individual skin phenotype and provides epidermal protection from various stimuli, such as ultraviolet irradiation, through a complex process called melanogenesis, which can be regulated by autocrine or paracrine factors. Recent evidence has revealed the paracrine effects of keratinocytes on melanogenesis by secreting cytokines, including α-melanocyte stimulating hormone and endothelin-1. In addition to keratinocytes, there are other types of cells in the skin, such as fibroblasts and immune cells, which are also actively involved in the regulation of melanocyte behaviour through the production of paracrine factors. In addition, extracellular matrix proteins, which are secreted mainly by skin-resident cells, not only play direct roles in regulating melanocyte morphology and functions but also provide structural support between the epidermis and dermis to control the distribution of various secreted cytokines from keratinocytes and/or fibroblasts, which are potentially involved in the regulation of melanogenesis. Moreover, understanding the origin of melanocytes (neural crest cells) and the presence of nerve endings in the epidermis can reveal the intimate contact between melanocytes and cutaneous specific nervous system proteins. Melanocytes are associated with all these networks with corresponding receptors expressed on the cell surface. In this review, we provide an overview of recent advances in determining the intimate relationships between melanocytes and their surrounding elements, which provide insights into the complex nature of the regulation of melanogenesis.