Proopiomelanocortin, Its Derived Peptides, and the Skin

Abstract

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.

Differential expression of HPA axis homolog in the skin

“…The skin also contains the full machinery for POMC processing (PC1, PC2 convertases and 7B2 protein) with generation of ACTH or α-MSH, and β-LPH or β-endorphin as final products, depending on the cellular compartment and cell type (Bohm et al, 2005;Luger et al, 1999;Paus et al, 1999;Slominski et al, 1999b;Slominski et al, 2004b;Slominski and Wortsman, 2000;Slominski et al, 2000d;Wintzen and Gilchrest, 1996). In human skin, the process can be upregulated by UVR and factors increasing cAMP levels, while it is inhibited by several growth factors (Luger et al, 1999;Slominski and Pawelek, 1998;Slominski et al, 2004b;Slominski et al, 2000d).…”

α-Melanocyte-Stimulating Hormone Inhibits Allergic Airway Inflammation

“…Originally, POMC was discovered in the pituitary gland, but subsequently, POMC-derived peptides were also detected in lymphocytes, monocytes, Langerhans cells, and epithelial cells (1)(2)(3)(4)(5).…”

What controls melanogenesis?

“…The cardinal question arises, what controls melanogenesis in individuals of different skin colors, considering zyme in the cascade of melanogenesis, where the amino acid L-tyrosine presents the crucial substrate to start that mRNA expression for tyrosinase is not different in white and black skin (11). this biosynthetic pathway with the formation of dopaquinone (2).…”

“…Of this, the tetrapeptide His-Phe-Argcan produce as well as secrete MSH and ACTH peptides (8)(9)(10)(11). Melanin pigmentation is defined here as a…”

“…Truncated forms of ACTH differ in their capacity to activate adenylate cyclase Accepting that the local cutaneous expression of POMC and the activation of corresponding receptors coupled to human MC-1, with some of them (ACTH [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17] ) being even more potent than a-MSH itself serve as important regulators of epidermal and hair (10) receptors (16)(17)(18)(19)27). The potential intracrine mechanism of action (cells that express intracellular MSH The expression and activity of MSH receptors can be regulated by environmental factors.…”