Figure 4.

Mechanisms of the physiologic tanning response. Hormonal interactions between epidermal keratinocytes and melanocytes mediate much of the cutaneous melanization response. DNA and cellular damage in keratinocytes up-regulates transcription of the pro-opiomelanocortin (POMC) gene which encodes production and secretion of melanocyte stimulating hormone (α-MSH). α-MSH binding to melanocortin 1 receptor (MC1R) on melanocytes in the basal epidermis generates the second messenger cAMP via interactions between MC1R and adenylyl cyclase, and leads to activation of protein kinase A and the cAMP responsive binding element (CREB) and microphthalmia (Mitf) transcription factors. CREB and Mitf directly enhance melanin production by raising levels of tyrosinase and other melanin biosynthetic enzymes. Thus, MSH-MC1R signaling leads to enhanced pigment synthesis by melanocytes and accumulation of melanin by epidermal keratinocytes. By this mechanism, the skin is better protected against UV insults. Of note, UV-induced pigmentation may also occur through other signaling pathways as well as direct effects of UV on melanocytes, and there is some disagreement in the field over the role of epidermal MSH in the adaptive pigmentary response.