Mouse Pattern Baldness: A Step Forward in Androgenetic Alopecia Research

Animal models of human medical conditions are valuable tools for biomedical research and preclinical drug discovery. Last year a group of hair growth scientists at Wyeth Research (now part of Pfizer) unveiled a strain of genetically altered mice that were developed to mimic the biology of androgenetic alopecia (AGA).1

The mice were genetically engineered to express the human androgen receptor (AR) gene in their hair follicle cells. AR is the receptor for dihydrotestosterone (DHT), the hormone implicated in male pattern hair loss (see our previous post on anti-androgens for more information on AR and DHT).

As expected, DHT inhibited hair regeneration in these mice. When a patch of hair was removed from the backs of the mice, DHT treatment significantly reduced the rate of hair regrowth, simulating the action of androgens in AGA (see a picture of the results here on the Endocrinology website).

The effect of DHT on hair regrowth was completely reversed by treatment with an AR antagonist (hydroxyflutamide) and was not observed in genetically normal mice, proving that DHT's effects on hair were dependent on AR. One notable difference between these mice and human patients with AGA is that the inhibition of hair regrowth by DHT was only a temporary delay, rather than a persistent lack of growth.

The authors go on to suggest that AR influences hair growth by affecting a cell signaling pathway known as the Wnt/β-catenin pathway, which is essential for hair follicle development and hair growth.2

Based on the observation that AR inhibits β-catenin signaling in other cell types,3, 4 this study suggests that DHT may interfere with hair growth by blocking the actions of β-catenin in the hair follicle.

In the future the group plans to directly test the role of β-catenin by introducing another genetic modification that would allow them to easily turn the pathway on and off during the hair regeneration process. The authors conclude that this “mouse model will be a valuable tool for elucidating the mechanisms responsible for androgen-AR-dependent hair loss and the development of effective treatments for hair loss in humans.”

A companion article in the same issue of Endocrinology shares the same optimism and enthusiasm: "the potential for AR blocking β-catenin actions is interesting given the evidence that hair follicle development and cycling is dependent on Wnt-β-catenin signaling... The new mouse model will permit further characterization of the mechanism by which androgens alter β-catenin activity."

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1. Crabtree JS, Kilbourne EJ, Peano BJ, Chippari S, Kenney T, McNally C, Wang W, Harris HA, Winneker RC, Nagpal S, Thompson CC. A mouse model of androgenetic alopecia. Endocrinology. 2010 May;151(5):2373-80. Link to Pubmed

2. Kishimoto J, Burgeson RE, Morgan BA. Wnt signaling maintains the hair-inducing activity of the dermal papilla. Genes Dev. 2000 May 15;14(10):1181-5. Link to Pubmed

3. Chesire DR, Isaacs WB. Ligand-dependent inhibition of beta-catenin/TCF signaling by androgen receptor. Oncogene. 2002 Dec 5;21(55):8453-69. Link to Pubmed

4. Pawlowski JE, Ertel JR, Allen MP, Xu M, Butler C, Wilson EM, Wierman ME. Liganded androgen receptor interaction with beta-catenin: nuclear co-localization and modulation of transcriptional activity in neuronal cells. J Biol Chem. 2002 Jun 7;277(23):20702-10. Link to Pubmed

5. Walker WH. Is the "comb over" dying? A mouse model for male pattern baldness (androgenic alopecia). Endocrinology. 2010 May;151(5):1981-3. Link to Pubmed