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 types, POMC can give rise to at least eight distinct peptides whose biologic roles are incompletely delineated. Although blood-borne pituitary-derived bioactivity for the skin was first recognized 80 years ago and the responsible neuropeptides isolated 20-40 years ago, our understanding of POMC-derived peptides in skin is still rapidly evolving. In particular, recent work in cultured human and murine skin-derived cells has demonstrated POMC gene expression as well as modulation of POMC and many of its derived peptides in response to physiologic signals including ultraviolet irradiation and cytokines. Immunoreactivity for these peptides has also been detected in normal skin and hair follicles, strongly suggesting cutaneous synthesis in vivo. Candidate autocrine or paracrine functions include enhanced melanogenesis, immunomodulation, and effects on cell cycle regulation and differentiated function in both the epidermis and its appendages. This article reviews recent data concerning POMC gene expression and regulation, protein processing, signal transduction, and biologic functions relevant to cutaneous biology.