MSH and its pigmentary role in mamals

Sir,

MSH stimulates melanosome dispersion in lower vertebrates and it is well recognized that in these animals it has an important role in the regulation of skin colour. Whether MSH has any physiological significance as a pigmentary hormone in mammals is, however, more debatable.
There is no doubt that MSH will stimulate coat darkening in a number of mammals through the mediation of cyclic AMP and the activation of tyrosinase, the key enzyme in the melanin pathway.
We have shown that in the hair follicular melanocytes of the C3H-HeAvy mouse MSH stimulates the synthesis of tyrosinase and this accounts for the increase in tyrosinase activity that is necessary for eumelanin synthesis (Burchill et al, 1987). Whether MSH can also increase the catalytic activity of tyrosinase through a post-translational effect, as it does in melanoma cells (Fuller et al, 1987) is not yet known.
Stimulation of eumelanin synthesis is not exclusive to MSH since other activators of the cyclic AMP system, such as beta-agonists, are also effective (Burchill & Thody, 1986a). Dopamine agonists (D2), on the other hand, depress tyrosinase levels and decrease eumelanin production (Burchill et al, 1986; Burchill & Thody, 1986b). Interestingly, despite the low levels of tyrosinase phaeomelanin synthesis continues (Burchill et al, 1986; Burchill & Tody, 1986b), It appears that phaeomelanin synthesis, in contrast to that of eumelanin, is less dependent upon tyrosinase and this could explain why MSH fails to stimulate its production (Burchill et al, 1986). The synthesis of phaeomelanin is thought to be regulated by a factor related to the product of the agouti gene and it is possible that MSH, in inducing the eumelanin synthesis, may actually depress its expression (Tamate & Takeuchi, 1984), Whatever the mechanism of action it seems that MSH is only able to induce eumelanin synthesis in hair follicular melanocytes of mice that express the agouti gene. For instance, Geschwind et al (1972) showed that MSH has no effect on hair follicular melanocytes of non-agouti mice and we have since confirmed this. Whether the agouti gene regulates MSH action in hair follicular melanocytes of other species is not yet known.
The agouti gene certainly does not have the same importance in epidermal melanocytes (Tamate et al, 1986). Different regulatory mechanisms may operate in epidermal melanocytes and apart from reports that MSH may enhance their differentiation in neonatal mice (Hirobe & Takeuchi, 1977), there is little evidence to suggest that epidermal melanocytes will respond to MSH (Nordlund et al, 1986; Seechurn & Thody, 1986). The same may also be true in man. Although high doses of MSH peptides may bring about skin darkening in man (Lerner & McGuire, 1964) human melanocytes in culture are unresponsive to MSH (Halaban et al, 1983; Friedmann & Gilchrest, 1987). We have also found no effects with either alpha-MSH or more potent analogues on tyrosinase in short term incubations of human skin. Furthermore, there seems to be no relationship between skin pigmentation and circulating levels of MSH peptides except when the levels are extremely high as in certain disorders of the pituitary adrenal axis (see Friedmann & Thody, 1986).
In conclusion it would appear that while MSH stimulates some pigment cells its pigmentary action is not as widespread as is commonly assumed. It may have a role in the regulation of coat colour in some species through its effect on hair follicular melanocytes but there is little evidence to suggest that is has any effect on epidermal melanocytes. In man UV is probably more important in the regulation of skin pigmentation, and any MSH-induced pigmentation is likely to be of pathological rather than physiological significance.

A.J. Thody and S.A. Burchill - Dept of Dermatology
University of Newcastle upon Tyne

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