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双氢睾酮通过Wnt/β-连环蛋白信号通路调控C57BL/6小鼠及器官培养中的毛发生长。

Dihydrotestosterone Regulates Hair Growth Through the Wnt/β-Catenin Pathway in C57BL/6 Mice and   Organ Culture.

作者信息

Chen Xianyan, Liu Ben, Li Ying, Han Le, Tang Xin, Deng Wenjia, Lai Wei, Wan Miaojian

机构信息

Department of Dermatology, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.

Department of Dermatology, Hexian Medical Affiliated Hospital of Southern Medical University, Guangzhou, China.

出版信息

Front Pharmacol. 2020 Jan 23;10:1528. doi: 10.3389/fphar.2019.01528. eCollection 2019.

Abstract

Dihydrotestosterone (DHT) is the most potent androgen that regulates hair cycling. Hair cycling involves cross-talk between the androgen and Wnt/β-catenin pathways. However, how DHT regulates hair follicle (HF) growth through the Wnt/β-catenin pathway has not been well investigated. This study aimed to investigate the roles of DHT in hair growth and . Human scalp HFs were treated with different concentrations of DHT (10, 10, 10, 10, and 10 mol/L) for 10 days. The effects of DHT on hair shaft elongation, the proliferation of hair matrix cells, and the levels of β-catenin, GSK-3β, and phosphorylated GSK-3β (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 β-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 and C57BL/6 mice. At 10 mol/L, DHT inhibited HF growth and β-catenin/p-GSK-3β expression, whereas 10 mol/L DHT induced HF growth and β-catenin/p-GSK-3β expression. In addition, a β-catenin inhibitor (21H7) inhibited HF growth , while a β-catenin activator (IM12) promoted HF growth 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/β-catenin pathway.

摘要

双氢睾酮(DHT)是调节毛发周期的最具活性的雄激素。毛发周期涉及雄激素与Wnt/β-连环蛋白信号通路之间的相互作用。然而,DHT如何通过Wnt/β-连环蛋白信号通路调节毛囊(HF)生长尚未得到充分研究。本研究旨在探讨DHT在毛发生长中的作用。将不同浓度(10⁻⁹、10⁻⁸、10⁻⁷、10⁻⁶和10⁻⁵mol/L)的DHT作用于人头皮毛囊10天。在培养的毛囊中评估DHT对毛干伸长、毛基质细胞增殖以及β-连环蛋白、糖原合成酶激酶-3β(GSK-3β)和磷酸化GSK-3β(ser9)水平的影响。在C57BL/6小鼠中进一步研究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-连环蛋白信号通路后,观察培养的人毛囊的生长情况。我们发现不同浓度的DHT对人毛囊和C57BL/6小鼠有不同影响。在10⁻⁵mol/L时,DHT抑制毛囊生长以及β-连环蛋白/p-GSK-3β表达,而10⁻⁹mol/L DHT诱导毛囊生长以及β-连环蛋白/p-GSK-3β表达。此外,β-连环蛋白抑制剂(21H7)抑制毛囊生长,而β-连环蛋白激活剂(IM12)促进毛囊生长并拮抗高水平DHT对毛囊的抑制作用。这些结果表明,DHT在区域特异性毛发生长中起关键作用,这可能与Wnt/β-连环蛋白信号通路有关。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7518/6989660/1027d773198d/fphar-10-01528-g001.jpg

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