Alpha-MSH causes a small rise in cAMP but has no effect on basal or ultraviolet-stimulated melanogenesis in human...

The effects of alpha-melanocyte stimulating hormone (alpha-MSH) were studied on levels of cyclic adenosine 3',5'-monophosphate (cAMP), melanin content and response to ultraviolet radiation (UVR) in cultured human melanocytes (HuMC). Foreskin HuMC were cultured in a hormone-supplemented system not dependent on the presence of phorbol esters. Following addition of alpha-MSH (10(-6) M) there was a rise in cAMP levels maximal between 5 and 15 min to 9.4 +/- 3.2 pM/10(5) cells, while control levels were 3.6 +/- 0.7 pM/10(5) cells. After 7 days' culture in the presence of alpha-MSH (10(-8) -10(-6) M) the melanin content increased by only 35%, whereas Forskolin (10(-5) M) induced a 9.5-fold rise in cAMP after 5 min and a 10.9-fold rise in melanin content after 7 days. When HuMC were irradiated daily for 6 days with UVR (Helarium fluorescent lamps emitting 20% UVB, 80% UVA) melanin content rose 2.7-fold (SE 0.3). This was unchanged or slightly reduced in the presence of alpha-MSH (10(-8)-10(-6) M). Parallel observations on Cloudman S91 melanoma cells showed that alpha-MSH caused only an 80% increase in melanin content after 4 days. The rise in melanin content induced by three daily UV-irradiations (2.4-fold, SE 0.5) was unchanged by alpha-MSH (10(-8)-10(-6) M). Although alpha-MSH induces a small rise in cAMP in HuMC this does not result in melanogenesis, and the response to UVR is not affected by alpha-MSH in either HuMC or S91 cells.