Androgen Modulation Of Wnt/β-catenin Signaling In Androgenetic Alopecia.

[Squeegee 2.0]

Premanand A1, Reena Rajkumari B2.
Author information

Abstract
Androgenetic alopecia (Androgenetic Alopecia) is a dermatological disorder of scalp hair loss characterized by a progressive miniaturization of hair follicles with shortened anagen phase leading to a decreased number of hairs on the scalp. It is a complex polygenic trait prevailing around two-thirds of the male population. Elevated expressions of 5α-dihydrotestosterone and androgen receptor are the causal factors for Androgenetic Alopecia. This review describes recent studies on the role of androgens and androgen receptor (AR) transactivation activity in modulating the Wnt/β-catenin signaling in the dermal papilla cells of the balding scalp in androgenetic alopecia. Here, we analyse the androgen-induced dermal papilla secreted factors on stimulating catagen entry in hair follicles and the molecular cross-talk between AR and Wnt/β-catenin signaling with a brief mention on alternative treatment strategy targeting Wnt/β-catenin signaling for promoting hair growth.

https://www.ncbi.nlm.nih.gov/pubmed/29549490

 

[Squeegee 2.0]

An investigation of crosstalk between Wnt/β-catenin and transforming growth factor-β signaling in androgenetic alopecia

Conclusions:
These data indicate that crosstalk between Wnt/β-catenin and TGF-β signaling pathways may exist as one of the important mechanisms contributing to Androgenetic Alopecia.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5265840/

 

[Squeegee 2.0]

Hair follicle stem cell differentiation is inhibited through cross-talk between Wnt/beta-catenin and androgen signalling in dermal papilla cells from patients with androgenetic alopecia

Hair follicle (HF) regeneration begins when signals from the mesenchyme-derived dermal papilla cells (DPC) reach multipotent epidermal stem cells in the bulge region. Wnt/β-catenin signalling is known to affect mammalian hair growth positively. In androgenetic alopecia (Androgenetic Alopecia), androgens cause HF miniaturization through a mechanism that remains unclear. Circulating androgens act on DPC and alter paracrine factors that influence hair epithelial cells. To elucidate the role of androgens in dermal papilla-induced differentiation of HF stem cells. HF stem cell differentiation was evaluated in a coculture model with DPC or culturing with media conditioned by DPC after activation of androgen and Wnt/β-catenin signalling pathways. To study the molecular cross-talk between the androgen and Wnt signalling pathway in DPC, we analysed the expression and activation of downstream Wnt signalling molecules in the presence of androgens. In a coculture model with human DPC from patients with Androgenetic Alopecia and HF stem cells, we observed that androgens abrogate hair differentiation evaluated by hair-specific keratin 6 expression. Wnt signalling activation restored the ability of androgen-treated DPC to induce differentiation. Androgen treatment revealed a significant decrease in the cytoplasmic/total β-catenin protein ratio and upregulation of the activity of glycogen synthase kinase-3β in DPC, indicative of canonical Wnt pathway inhibition. These results suggest that androgens deregulate DPC-secreted factors involved in normal HF stem cell differentiation via the inhibition of the canonical Wnt signalling pathway.

https://www.researchgate.net/public...ells_from_patients_with_androgenetic_alopecia

 

[Squeegee 2.0]

Minoxidil activates β-catenin pathway in human dermal papilla cells: a possible explanation for its anagen prolongation effect.
Kwack MH1, Kang BM, Kim MK, Kim JC, Sung YK.
Author information

Abstract
BACKGROUND:
It is believed that the length of the actively growing phase of the anagen hair cycle mainly contributes to hair length. Recent studies showed that maintenance of β-catenin activity in the dermal papilla cells (DPCs) enables hair follicles to keep actively growing. Topical minoxidil treatment promotes hair growth in men with androgenetic alopecia, suggesting that minoxidil may prolong the actively growing phase of the anagen hair cycle.

OBJECTIVE:
To investigate whether minoxidil prolongs the anagen hair cycle in mice and, if so, to investigate whether minoxidil activates β-catenin pathway in human DPCs.

METHODS:
Dorsal skins of C57BL/6 mice were depilated to synchronize the hair cycle. After 10 days, 3% minoxidil were topically applied daily for 10 days. Sections of back skins were stained with hematoxylin and eosin. Hair follicles were graded and hair cycle score (HCS) was calculated. Cultured human DPCs were transiently transfected with the β-catenin responsive TCF reporter plasmid (pTopflash) and corresponding negative control reporter (pFopflash) to assess the activity of β-catenin signaling by minoxidil. Immunofluorescence staining and immunoblot were performed to examine the expression and localization of β-catenin in the presence or absence of minoxidil. Phosphorylation of GSK3β, PKA and PKB were also examined by immunoblot after minoxidil treatment. RT-PCR analysis and immunoblot were employed to investigate the expression of β-catenin pathway targets in DPCs, such as Axin2, Lef-1, and EP2.

RESULTS:
Modest extension of anagen phase thereby delay of catagen progression was observed by application of minoxidil in mice. Minoxidil stimulated the transcriptional activity of pTopflash but not pFopflash. Nuclear accumulation of β-catenin was also observed after minoxidil treatment. Immunoblot further showed that minoxidil treatment increases the phosphorylation of GSK3β, PKA and PKB. Moreover, minoxidil induced Axin2, Lef-1, and EP2 expression.

CONCLUSION:
Our results strongly suggest that minoxidil extends the anagen phase by activating β-catenin activity in the DPCs.

https://www.ncbi.nlm.nih.gov/pubmed/21524889

 

[Squeegee 2.0]

5α-dihydrotestosterone and the Wnt/β-catenin pathway in Danio rerio ovarian tissue following 2 and 4 hour incubations

https://soundideas.pugetsound.edu/c...sredir=1&article=1305&context=summer_research

 

[Squeegee 2.0]

Assessment of tissue levels of dickkopf‐1 in androgenetic alopecia and alopecia areata

Background
Androgenetic alopecia (Androgenetic Alopecia) is the commonest form of hair loss in men. Alopecia areata (AA) is an organ‐specific autoimmune disease. Studies revealed that Dickkopf 1 (DKK‐1), a powerful suppressor of the Wnt/β‐catenin signaling pathway, induced anagen‐to‐catagen transition in mice. Moreover, in vitro studies suggested that DKK‐1 played a role in dihydrotestosterone (DHT)‐induced balding.

Aim
To evaluate the tissue levels of DKK‐1 in patients with Androgenetic Alopecia and AA, to assess its possible role as a pathogenetic mechanism in both disorders.

Methods
This study included 24 patients with Androgenetic Alopecia, 31 patients with AA, and 33 healthy controls. Scalp biopsies were taken from all participants for the detection of tissue DKK‐1 levels.

Results
Tissue DKK‐1 levels were significantly higher in patients with Androgenetic Alopecia than in controls (P = 0.000) as well as in patients with AA than in controls (P = 0.001). In addition, they were significantly higher in patients with Androgenetic Alopecia than in patients with AA (P = 0.000). DKK‐1 was higher in male than in female patients with Androgenetic Alopecia. DKK‐1 was negatively correlated with disease duration in Androgenetic Alopecia.

Conclusion
In conclusion, this study suggests an important role for DKK‐1 in the pathogenesis of Androgenetic Alopecia and AA through documenting higher tissue DKK‐1 levels in patients with both hair disorders compared to controls and suggests that DKK‐1 may be a promising therapeutic target for these hair diseases.

https://onlinelibrary.wiley.com/doi/abs/10.1111/jocd.12171

 

[Squeegee 2.0]

Distinct functions for Wnt/β-catenin in hair follicle stem cell proliferation and survival and interfollicular epidermal homeostasis

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3900235/