Tyrosinase: a developmentally specific major determinant of peripheral dopamine
Tyrosinase: a developmentally specific major determinant of peripheral dopamine
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DOI：
10.1096/fj.02-0736com
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发表时间：
2003-07-01
期刊：
影响因子：
4.8
通讯作者：
Hearing, VJ
中科院分区：
文献类型：
--
作者：
Eisenhofer, G;Tian, H;Hearing, VJ
L-3，4-二羟基苯丙氨酸是多巴胺的直接前体，可由两种酶形成：产生儿茶酚胺的神经元和嗜铬细胞中的酪氨酸羟化酶（TH）和黑素细胞中的酪氨酸酶。在这项研究中，我们研究了酪氨酸酶是否有助于多巴胺的产生。TH的缺乏引起显着减少去甲肾上腺素在白化病和有色15日龄小鼠。与此相反，外周多巴胺水平降低，只有在白化病TH缺陷小鼠和色素高于白化病小鼠，无论TH的存在或不存在。接下来，我们研究了白化病和色素TH野生型小鼠多巴胺和酪氨酸酶和黑色素皮肤表达的年龄相关变化。我们发现，随着年龄的增长，酪氨酸酶的表达和功能发生变化，色素和白化病小鼠外周多巴胺的差异消失。在年轻动物中，酪氨酸酶存在于表皮中，但不产生可检测的黑色素。随着年龄的增长，酪氨酸酶仅局限于毛囊周围，黑色素合成变得更加明显，多巴胺合成减少。这些数据揭示了一个以前未被认识的TH-独立的主要途径外周多巴胺合成的年轻，但不是成年小鼠。这种多巴胺来源的短暂性质反映了酪氨酸酶依赖的多巴胺产生到黑色素产生的发育转换。
L-3,4-dihydroxyphenylalanine, the immediate precursor of dopamine, can be formed by two enzymes: tyrosine hydroxylase (TH) in catecholamine-producing neurons and chromaffin cells and tyrosinase in melanocytes. In this study we examined whether tyrosinase contributes to production of dopamine. Deficiency of TH caused marked reductions in norepinephrine in albino and pigmented 15-day-old mice. In contrast, peripheral levels of dopamine were reduced only in albino TH-deficient mice and were higher in pigmented than in albino mice, regardless of the presence or absence of TH. We next examined age-related changes in dopamine and cutaneous expression of tyrosinase and melanin in albino and pigmented TH wild-type mice. We found that the differences in peripheral dopamine between pigmented and albino mice disappeared with advancing age following changes in expression and function of tyrosinase. In young animals, tyrosinase was present in epidermis but did not produce detectable melanin. With advancing age, tyrosinase was localized only around hair follicles, melanin synthesis became more pronounced, and dopamine synthesis decreased. The data reveal a previously unrecognized TH-independent major pathway of peripheral dopamine synthesis in young, but not adult, mice. The transient nature of this source of dopamine reflects a developmental switch in tyrosinase-dependent production of dopamine to production of melanin.