Dihydrotestosterone Regulates Hair Growth Through the Wnt/β-Catenin Pathway in C57BL/6 Mice and In Vitro Organ Culture
Dihydrotestosterone Regulates Hair Growth Through the Wnt/β-Catenin Pathway in C57BL/6 Mice and In Vitro Organ Culture
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二氢睾酮通过 C57BL/6 小鼠和体外器官培养中的 Wnt/β-连环蛋白途径调节毛发生长
DOI：
10.3389/fphar.2019.01528
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发表时间：
2020-01-23
影响因子：
5.6
通讯作者：
Wan, Miaojian
中科院分区：
文献类型：
--
作者：
Chen, Xianyan;Liu, Ben;Wan, Miaojian
双氢睾酮（DHT）是调节头发周期的最有效的雄激素。毛发循环涉及雄激素和Wnt/β-连环蛋白途径之间的相互作用。然而，DHT如何通过Wnt/β-catenin途径调节毛囊（HF）生长尚未得到很好的研究。本研究旨在探讨双氢睾酮在体内和体外毛发生长中的作用。用10（-5）、10（-6）、10（-7）、10（-8）和10（-9）mol/L的DHT处理人头皮HFs 10天。在培养的HFs中评价DHT对毛干伸长、毛基质细胞增殖以及β-连环蛋白、GSK-3 β和磷酸化GSK-3 β（ser 9）水平的影响。在C57 BL/6小鼠中进一步研究了DHT的作用。此外，在存在或不存在DHT的情况下，通过抑制剂或激活剂干扰β-连环蛋白途径后，观察到培养的人HF的生长。结果发现，不同浓度的DHT对体外培养的人成纤维细胞和C57 BL/6小鼠的成纤维细胞有不同的影响。在10（-6）mol/L时，DHT抑制HF生长和β-catenin/p-GSK-3 β表达，而10（-7）mol/L DHT诱导HF生长和β-catenin/p-GSK-3 β表达。此外，β-连环蛋白抑制剂（21 H7）在体外抑制HF生长，而β-连环蛋白激活剂（IM 12）在体外促进HF生长，并拮抗高水平的DHT对HF的抑制。这些结果表明，DHT在区域特异性毛发生长中起着关键作用，这可能与Wnt/β-catenin通路有关。
Dihydrotestosterone (DHT) is the most potent androgen that regulates hair cycling. Hair cycling involves cross-talk between the androgen and Wnt/beta-catenin pathways. However, how DHT regulates hair follicle (HF) growth through the Wnt/beta-catenin pathway has not been well investigated. This study aimed to investigate the roles of DHT in hair growth in vivo and in vitro. Human scalp HFs were treated with different concentrations of DHT (10(-5), 10(-6), 10(-7), 10(-8), and 10(-9) mol/L) for 10 days. The effects of DHT on hair shaft elongation, the proliferation of hair matrix cells, and the levels of beta-catenin, GSK-3 beta, and phosphorylated GSK-3 beta (ser9) were evaluated in the cultured HFs. The effects of DHT were further investigated in C57BL/6 mice. Moreover, the growth of cultured human HFs was observed after interfering with the beta-catenin pathway through inhibitors or activators in the presence or absence of DHT. We found that different concentrations of DHT had different effects on human HFs in vitro and C57BL/6 mice. At 10(-6) mol/L, DHT inhibited HF growth and beta-catenin/p-GSK-3 beta expression, whereas 10(-7) mol/L DHT induced HF growth and beta-catenin/p-GSK-3 beta expression. In addition, a beta-catenin inhibitor (21H7) inhibited HF growth in vitro, while a beta-catenin activator (IM12) promoted HF growth in vitro and antagonized the inhibition of HFs by high levels of DHT. These results suggest that DHT plays a pivotal role in region-specific hair growth, which may be related to the Wnt/beta-catenin pathway.