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Skin tyrosinase activity increases during hair growth in C3H–HeA*vymice 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 α-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 α-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 α-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 α-MSH and other activators of the cyclic AMP system during periods of phaeomelanin production.J. Endocr.(1986) 111,225–232

Skin tyrosinase levels and the eumelanin and phaeomelanin contents of the hair were measured in pubertal and adult C3H–HeA*vymice that grow dark and golden yellow hair respectively. Hair growth was initiated by plucking and the skin tyrosinase levels, which increased during the growth of new hair and peaked at around 9 days after plucking, were higher during the growth of dark hair in the pubertal mice than during the growth of yellow hair in the adult mice. Although there was only a twofold difference in the phaeomelanin contents of these two types of hair, the dark hair of the pubertal mice contained over 20 times more eumelanin than the golden-yellow hair of the adult mice. These results suggest that the changes in coat colour in C3H–HeA*vymice are due mainly to changes in eumelanin synthesis by the hair follicular melanocytes and that the production of this pigment requires higher levels of the enzyme tyrosinase than does the production of phaeomelanin. These changes did not appear to be related to plasma α-MSH levels. Nevertheless, administration of α-MSH increased skin tyrosinase activity in the pubertal mice that were growing dark hair and produced a twofold increase in the eumelanin content of the hair. However, it had no such effects in adult mice and also failed to affect the phaeomelanin content of the hair in both groups of mice. In contrast to α-MSH, bromocriptine decreased skin tyrosinase levels and the eumelanin content and increased the phaeomelanin content of the hair in pubertal mice. These effects of bromocriptine were unrelated to plasma immunoreactive α-MSH levels and were not restored when α-MSH was administered together with the dopamine agonist.Although the present results support the idea that α-MSH increases coat darkening in the C3H–HeA*vymouse through its actions on tyrosinase activity and eumelanin synthesis, it seems that these actions are more dependent on changes at the melanocyte level than changes in circulating α-MSH. The present results further suggest that dopaminergic mechanisms may also play a direct regulatory role in the control of coat colour in this mouse.J. Endocr.(1986) 109,15–21

Bromocriptine, a dopamine agonist that blocks the secretion of MSH, inhibits melanogenesis in the hair follicular melanocytes of pubertal C3H–HeA*vymice. However, since this effect cannot be explained by a reduction in circulating α-MSH, we have examined the possibility that dopaminergic mechanisms may have a direct inhibitory effect on these melanocytes.Bromocriptine decreased tyrosinase activity in skin explants from 30- to 35-day-old mice that were growing dark hair. This decrease in tyrosinase activity was blocked by dopamine receptor antagonists, haloperidol or spiperone. The specific D2agonist LY 171555 also inhibited tyrosinase activity in the skin explants in a dose-related manner and the effect was blocked by sulpiride, a D2-receptor antagonist. Neither bromocriptine nor LY 171555 had any effect on tyrosinase activity in skin explants taken from adult mice that were growing yellow hair. The D1-receptor agonist SKF 38393 had no effect on tyrosinase activity in skin explants from either group of mice.The present results support the idea that dopamine D2-receptor agonists have a direct inhibitory effect upon tyrosinase activity of hair follicular melanocytes of the C3H–HeA*vymouse. However, this effect was confined to periods of dark hair growth when the melanocytes produce eumelanin. The D2agonists were ineffective in reducing tyrosinase activity during adult life when the melanocytes produce predominantly phaeomelanin. This suggests that different control mechanisms may operate in the hair follicular melanocytes during periods of eumelanin and phaeomelanin synthesis.J. Endocr.(1986) 111,233–237

In this study, the effect of α-MSH on tyrosinase activity was compared in epidermal and hair follicular melanocytes of mice. It had no effect on epidermal tyrosinase activity in dorsal skin from neonatal non-agouti black mice (C57BL/6J) in both in-vivo and in-vitro experiments. Theophylline and 8-bromocyclic (c)AMP were similarly without effect in in-vitro experiments. In-vivo administration of α-MSH and theophylline for 7 days was also without effect on epidermal tyrosinase activity in ear skin of adult non-agouti mice, and the same was true for α-MSH in wild-type agouti mice. Activation of the epidermal melanocytes in the non-agouti and wild-type agouti mice with ultraviolet radiation also failed to bring about a response to α-MSH and to theophylline in the case of the former. No tyrosinase activity was detected in the epidermis of viable yellow mice (C3H-HeAvy), but, as shown previously, tyrosinase activity was present in the hair follicle when the hair was actively growing and was increased in those mice given either α-MSH or theophylline. α-MSH and theophylline had no such effects on hair follicular tyrosinase activity in the non-agouti mice.The present results suggest that α-MSH- and cAMP-dependent mechanisms have little or no importance in the regulation of tyrosinase expression in mouse epidermal melanocytes. α-MSH may, however, regulate tyrosinase expression in hair follicular melanocytes, but even in these melanocytes its action may be restricted to mice that express the agouti gene.J. Endocr. (1988) 119,517–522

Tyrosinase activity was increased in hair follicular melanocytes of C3H-HeAvymice during the hair cycle and reached higher levels on days 6–8 after plucking than on day 12. Similarly, the rate of incorporation of [35S]methionine into tyrosinase was greater on days 6–8 than on day 12, but the relative difference was much less. α-MSH had no effect on tyrosinase activity or the rate of [35S]methionine incorporation on day 12 and, while it increased both on days 6 and 8, it had a greater effect upon the latter. Pulse-chase experiments showed that the half-life of tyrosinase was 3·5 h and that this was unaffected by α-MSH.The results indicate that the increases in tyrosinase activity which occur during the hair cycle involve changes in both the synthesis and activation of the enzyme and that the predominant effect of α-MSH is on the former of these two processes.J. Endocr.(1988) 116,17–23