Proopiomelanocortin Gene Product Regulation in Keratinocytes

Proopiomelanocortin (POMC) is the precursor for adrenocorticotropic hormone, melanocyte-stimulating hormones, β-lipotropic hormone (βLPH), and β-endorphin. These peptides can function as neurotransmitters, modulate immune responses, and affect melanogenesis. We investigated POMC expression and protein processing in normal human keratinocytes. On Northern blot analysis, the baseline expression of the 1.2-kb POMC transcript was upregulated by ultraviolet radiation (UVR) or by stimulation with interleukin-1α (IL-1α) or phorbol 12-tetradecanoate 13-acetate (TPA). On Western blot analysis, POMC, βLPH, and β-endorphin were detected in cell extracts under baseline conditions. βLPH level increased substantially after UVR, IL-1α, or TPA. Within 36h after TPA stimulation, β-endorphin became undetectable in cell extracts, coinciding with an increase of β-endorphin-immunoreactive protein in the culture medium. Our data establish that keratinocytes synthesize POMC protein as well as its derivatives β-LPH and β-endorphin, and that this process is modulated by TPA, IL-1α, and UVR. βLPH and β-endorphin of keratinocyte origin may thus be involved in melanogenesis and/or immiunomodulation in the skin after sun exposure, and their release into the circulation may also have systemic effects.