MITOGENIC AND MELANOGENIC STIMULATION OF NORMAL HUMAN MELANOCYTES BY MELANOTROPIC PEPTIDES

The significance of melanotropic hormones as physiologic regulators of cutaneous pigmentation in humans is still controversial. Until recent ly, no direct effect for melanotropins could be demonstrated on human melanocytes, Here we present conclusive evidence that alpha-melanotrop in (alpha-melanocyte-stimulating hormone, alpha-MSH) and the related h ormone corticotropin (adrenocorticotropic hormone, ACTH) stimulate the proliferation and melanogenesis of human melanocytes maintained in cu lture in a growth medium lacking any AMP inducer. The minimal. effecti ve dose of either hormone is 0.1 nM. In time-course experiments, the i ncrease in cell number and tyrosinase activity became evident after on e treatment of the melanocytes with 100 nM alpha-MSH for 48 hr. The mi togenic effect gradually increased to 50-270% above control, depending on the individual melanocyte strain, with continuous treatment with 1 00 nM alpha-MSH for 8 days, whereas the melanogenic effect became maxi mal (70-450% increase above control) after 4 days of treatment. Wester n blot analysis of tyrosinase and the tyrosinase-related proteins TRP- 1 and TRP-2 revealed that alpha-MSH increased the expression of those three melanogenic proteins, This was not accompanied by any change in their mRNA levels after brief (1.5-24 hr) or prolonged (6 days) treatm ent with 100 nM alpha-MSH, suggesting that the increased expression of these melanogenic proteins was due to posttranscriptional events. The se results demonstrate both mitogenic and melanogenic effects of alpha -MSH and ACTH on human melanocytes. That both hormones are effective a t subnanomolar concentrations, combined with the presence of melanotro pin receptors on human melanocytes, strongly suggests that these melan otropins play a physiologic role in regulating human cutaneous pigment ation.