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/b-catenin pathways. However, how DHT regulates hair follicle (HF) growth through the Wnt/b-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 b-catenin, GSK-3b, and phosphorylated GSK-3b (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 bcatenin 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 b-catenin/p-GSK-3b expression, whereas 10-7 mol/L DHT induced HF growth and b-catenin/p-GSK-3b expression. In addition, a bcatenin inhibitor (21H7) inhibited HF growth in vitro, while a b-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/b-catenin pathway.

Alleviation of Androgenetic Alopecia with Aqueous Paeonia lactiflora and Poria cocos Extract Intake through Suppressing the Steroid Hormone and Inflammatory Pathway

“…In this study, after topical application of testosterone propionate solution, the dorsal hair growth by C57BL/6 mice was inhibited by disturbing the synchronized growth cycle at the initial stage [40]. Changes in the hair growth cycle resulted in skin color changes from fleshy pink to gray and black, as previously described [30,41]. In the present study, after C57BL/6 mice had ingested PL, hair growth in dorsal skin was quickly started, and the numbers and sizes of hair follicles increased, suggesting that hair quickly entered the growth phase.…”

“…The potentiation of Akt and GSK-3β phosphorylation improved Wnt signaling to protect against hair loss induced by testosterone. Finasteride provides a recognized treatment for AGA [6,41,45] and has also been used to treat prostate cancer [46]. We demonstrated that finasteride had no apparent effect on hair growth during the early stage of the experiment, but that subsequently, it quickly promoted hair growth.…”

Molecular Pathways Involved in Promoting Activity of Timosaponin BII on Hair Growth in C57BL/6 Mice

“…The relative expression levels of β -catenin, Wnt3a, and Wnt10b were analyzed by the Image Pro-Plus 6.0 software. Briefly, images were converted into a black and white mode at first; then, the integrated optical density (IOD) and the area of the positive region (AREA) were calculated; finally, the mean density is obtained as IOD/AREA to indicate the relative expression levels [ 21 ].…”

Perspectives on miRNAs Targeting DKK1 for Developing Hair Regeneration Therapy

“…Interestingly, apart from the mentioned involvements in various physiological conditions, dysregulation of Wnt/β-catenin signaling is strongly associated with the development of AGA—a dermatological disorder whereby the hair is abnormally shed from the skin where it normally should be presented. Particularly, it is suppressed in AGA [ 13 , 22 , 24 , 25 , 26 , 27 ]. Indeed, various Wnt proteins play a substantial role in the hair growth cycle [ 2 ].…”