Hair Loss

Endocrinology. 2010 Mar 16.

A Mouse Model of Androgenetic Alopecia ( Pattern Hair Loss )
Crabtree JS, et al

Androgenetic alopecia (AGA), commonly known as male pattern baldness, is a form of hair loss that occurs in both males and females. Although the exact cause is unknown, pattern hair loss is associated with genetic predisposition through traits related to androgen synthesis/metabolism and androgen signaling mediated by the androgen receptor (AR). Current therapies for AGA show limited efficacy at hair regrowth and are often associated with undesirable side effects. A major hurdle to developing new therapies for male pattern hairloss is the lack of small animal models to support hair loss drug discovery research. Here, we report the first rodent model of pattern hair loss. Previous work demonstrating that the interaction between androgen-bound AR and beta-catenin can inhibit Wnt signaling led us to test the hypothesis that expression of AR in hair follicle cells could interfere with hair regrowth in an androgen-dependent manner. Transgenic mice overexpressing human AR in the skin under control of the keratin 5 promoter were generated. Keratin 5-human AR transgenic mice exposed to high levels of 5 alpha-dihydrotestosterone (DHT) showed delayed hair regeneration, mimicking the AGA scalp. This effect is AR mediated, because treatment with the androgen receptor antagonist hydroxyflutamide inhibited the effect of dihydrotestosterone on hair regrowth. These results support the hypothesis that androgen-mediated hair loss is androgen receptor dependent and suggest that AR and beta-catenin mediate this effect. These mice can now be used to test new therapeutic agents for hair loss treatment, accelerating the drug discovery process.