PROOPIOMELANOCORTIN, ITS DERIVED PEPTIDES AND THE SKIN

`Proopiomelanocortin (POMC) is a protein synthesized predominately in the pituitary gland but also in a variety of other tissues, including the skin. Through enzyme-mediated cleavage that varies among cell type s, POMC can give rise to at least eight distinct peptides whose biolog ic roles are incompletely delineated, Although blood-borne pituitary-d erived bioactivity for the skin was first recognized 80 years ago and the responsible neuropeptides isolated 20-40 years ago, our understand ing of POMC-derived peptides in skin is still rapidly evolving. In par ticular, recent work in cultured human and murine skin-derived cells h as demonstrated POMC gene expression as well as modulation of POMC and many of its derived peptides in response to physiologic signals inclu ding ultraviolet irradiation and cytokines. Immunoreactivity for these peptides has also been detected in normal skin and hair follicles, st rongly suggesting cutaneous synthesis in vivo. Candidate autocrine or paracrine functions include enhanced melanogenesis, immunomodulation, and effects on cell. cycle regulation and differentiated function in b oth the epidermis and its appendages. This article reviews recent data concerning POMC gene expression and regulation, protein processing, s ignal transduction, and biologic functions relevant to cutaneous biolo gy.