Mitogenic and melanogenic stimulation of normal human melanocytes by melanotropic peptides.

Abstract

The significance of melanotropic hormones as physiologic regulators of cutaneous pigmentation in humans is still controversial. Until recently, no direct effect for melanotropins could be demonstrated on human melanocytes.Here we present conclusive evidence that a!-melanotropin (a-melanocyte-stimulating hormone, ai-MSH) and the related hormone corticotropin (adrenocorticotropic hormone, ACTH) stimulate the proliferation and melanogenesis of human melanocytes maintained in culture in a growth medium lacking any AMP inducer. The minimal effective dose of either hormone is 0.1 nM. In time-course experiments, the increase in cell number and tyrosinase activity became evident after one treatment of the melanocytes with 100 nM a-MSH for 48 hr. The mitogenic effect gradually increased to 50-270S% above control, depending on the individual melanocyte strain, with continuous treatment with 100 nM a-MSH for 8 days, whereas the melanogenic effect became maximal (70-450% increase above control) after 4 days oftreatment. Western blot analysis of tyrosinase and the tyrosinase-related proteins TRP-1 and TRP-2 revealed that a-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) treatment with 100 nM a-MSH, suggesting that the increased expression of these melanogenic proteins was due to posttranscriptional events. These results demonstrate both mitogenic and melanogenic effects of a-MSH and ACTH on human melanocytes. That both hormones are effective at subnanomolar concentrations, combined with the presence of melanotropin receptors on human melanocytes, strongly suggests that these melanotropins play a physiologic role in regulating human cutaneous pigmentation.a-Melanotropin (a melanocyte-stimulating hormone, a-MSH) is the physiologic hormone that regulates integumental pigmentation of many vertebrate species. For example, a-MSH induces rapid skin darkening in amphibians and reptiles and stimulates follicular eumelanogenesis in the mouse (1,2). In addition to the pigmentary effects, other functions for a-MSH and related melanotropins have been described, such as the antagonistic interaction with interleukin 1 (3, 4) and trophic effects on neurons (5, 6

Transforming Growth Factor-β1 Inhibits Basal Melanogenesis in B16/F10 Mouse Melanoma Cells by Increasing the Rate of Degradation of Tyrosinase and Tyrosinase-related Protein-1

“…Similar observations have been reported by others for melanocytes treated with a variety of agents able to modulate melanogenesis. For instance, Abdel-Malek et al (55) have shown that normal human melanocytes respond to ␣-MSH by increasing the intracellular protein levels of tyrosinase, TRP-1, and TRP-2 without any noticeable effect on their mRNA, even after prolonged treatments.…”

Involvement of Microphthalmia in the Inhibition of Melanocyte Lineage Differentiation and of Melanogenesis by Agouti Signal Protein

“…In humans, the mechanism that controls the class of melanin synthesized (eumelanin or pheomelanin) has not been elucidated. It is well established that ␣MSH increases the synthesis of eumelanin in human melanocytes (18,20,21). A human homologue for the mouse agouti locus has been cloned and its product functions similarly to the mouse protein in vivo and in vitro (22,23); however, its physiological function in humans remains to be elucidated.…”

Inhibitory Mechanism of an Extract of Althaea officinalis L. on Endothelin-1-Induced Melanocyte Activation.

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When the skin is irradiated with UVB light, various cytokines are released, act on normal human melanocytes (NHMC), and induce them to synthesize melanin pigment, to proliferate and to differentiate, which leads to increased pigmentation.1-3) Endothelin-1 (ET-1), 2,4) basic fibroblast growth factor (b-FGF), 5) and a-melanocyte-stimulating hormone, [6][7][8] all of which are produced by normal human keratinocytes (NHKC) and are up-regulated following UVB irradiation, act as mitogens for NHMC. Furthermore, an increase in ET-1 expression 3) in human skin after UVB irradiation has also been reported, and it has been suggested that ET-1 plays an important role in UVB-induced pigmentation.

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