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

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 <i>in vivo</i> and <i>in vitro</i>. 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 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 <i>in vitro</i> and C57BL/6 mice. At 10^-6 mol/L, DHT inhibited HF growth and β-catenin/p-GSK-3β expression, whereas 10^-7 mol/L DHT induced HF growth and β-catenin/p-GSK-3β expression. In addition, a β-catenin inhibitor (21H7) inhibited HF growth <i>in vitro</i>, while a β-catenin activator (IM12) promoted HF growth <i>in vitro</i> 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.