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

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

doi:10.3389/fphar.2019.01528

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 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 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 in vitro 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 in vitro, while a β-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/β-catenin pathway.

Highlights

Many hormones participate in the regulation of hair follicle (HF) growth and cycling, of which androgens are the most representative(Al-Nuaimi et al, 2010; Inui and Itami, 2013)
We evaluated the effects of DHT on human HF growth based on growth rate, morphology of the hair matrix (HM) and the dermal papilla (DP), and HF proliferative activity
Studies have found that 5areductase type 2 (5aR2) is more highly expressed in the androgenetic alopecia (AGA) balding scalp and beard HFs in males than in nonbalding AGA scalps (Price, 1999), so we speculated that the regionspecific expression of 5aR2 induces the distinct effects of androgens on HF growth

Summary

Introduction

Many hormones participate in the regulation of hair follicle (HF) growth and cycling, of which androgens are the most representative(Al-Nuaimi et al, 2010; Inui and Itami, 2013). In 1996, Itami showed that a higher level of 5areductase type 2 (5aR2) was found in balding scalp HFs than in occipital scalp HFs, which can convert T to the more potent DHT (Itami et al, 1996) This finding indicates that balding scalp HFs have a higher level DHT than nonbalding scalp HFs, which is consistent with the results of a double-blind study showing that DHT levels were significantly higher in a bald scalp than in a hair-containing scalp (Dallob et al, 1994). Once 5aR2 is inhibited by finasteride, an oral drug that can decrease both serum and scalp skin DHT levels, AGA progression is delayed (Drake et al, 1999; Price, 1999). These findings suggest that androgens are required to maintain AGA balding

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