Melanocyte-stimulating hormone and the regulation of tyrosinase activity in hair follicular melanocytes of the mouse.

Skin tyrosinase activity increases during hair growth in C3H-HeAvy mice and reaches higher levels in young (30- to 35-day-old) mice when the hair follicular melanocytes synthesize the black pigment, eumelanin, than in older (6-month-old) mice when they produce the golden yellow pigment, phaeomelanin. To examine the regulation of the melanocytes at these different stages we have compared the effect of alpha-MSH and other agents that act, through cyclic AMP-dependent mechanisms, on skin tyrosinase activity in both young and old mice during hair growth, initiated by plucking. Daily administration of alpha-MSH, isoprenaline or theophylline increased coat darkness, and skin tyrosinase activity in the younger mice 7-9 days after plucking, but they were ineffective in the older mice. Similarly alpha-MSH, 8-bromo-cyclic AMP or theophylline increased tyrosinase activity in skin explants from the younger mice incubated for up to 24 h but had no effect in explants from older mice. Cyclic GMP had no effect on tyrosinase activity in skin explants from both young and old mice. It is suggested that whereas cyclic AMP-dependent mechanisms may operate to regulate tyrosinase activity in the hair follicular melanocytes of younger mice that produce eumelanin these systems may not operate in the older mice when these melanocytes synthesize phaeomelanin. Phaeomelanin synthesis, unlike that of eumelanin, may not depend upon tyrosinase and its regulation by cyclic AMP and this could explain the low levels of this enzyme in the skin and its failure to respond to alpha-MSH and other activators of the cyclic AMP system during periods of phaeomelanin production.