A Mouse Model of Androgenetic Alopecia

Abstract

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 of AGA is not known, it 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 and are often associated with undesirable side effects. A major hurdle to developing new therapies for AGA is the lack of small animal models to support drug discovery research. Here, we report the first rodent model of AGA. 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 growth 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 5alpha-dihydrotestosterone showed delayed hair regeneration, mimicking the AGA scalp. This effect is AR mediated, because treatment with the AR antagonist hydroxyflutamide inhibited the effect of dihydrotestosterone on hair growth. These results support the hypothesis that androgen-mediated hair loss is AR dependent and suggest that AR and beta-catenin mediate this effect. These mice can now be used to test new therapeutic agents for the treatment of AGA, accelerating the drug discovery process.

Increased androgen receptor messenger RNA in frontal-parietal hair follicles of women with androgenetic alopecia

“…Therefore, the predominant action of androgens through ARs suggests the potential involvement of AR expression in hair follicles in the pathogenetic development of alopecia (Inui and Itami, 2001). Animal studies have demonstrated that androgens are responsible for growth delay in new hair follicles, acting through the AR pathway (Crabtree et al, 2010). In the present study, the AGA group displayed increased AR expression in the FP region not observed in normal controls, confirming the role of androgen hypersensitivity in this region.…”

Sex steroid synthesis in human skin in situ: The roles of aromatase and steroidogenic acute regulatory protein in the homeostasis of human skin

“…This enzyme was reported to be localized in the ORS and in the epidermis (Bayne et al, 1999). In addition, ORS-specific androgen receptor transgenic mice have been reported to mimic androgenetic alopecia characterized by delayed hair regeneration (Crabtree et al, 2010), suggesting that ORS and epidermis potentially play important roles in the androgen synthesis and/or action well-associated with hair growth. Thus, we examined the correlation between the hair density and the StAR expression levels in this study.…”

The Hair Growth‐Promoting Effect of Rumex japonicus Houtt. Extract

“…However, the efficacy disappears within a few months after stopping therapy and side effects are reported to cause allergic dermatitis and mild scalp irritation. Use of two drugs is limited by low efficacy and unfavorable effect [7]. Therefore, the interest and importance to develop novel preventive and/or therapeutic materials for hair loss have increased recently.…”