Development and Validation of Androgen-induced Hair Loss and Anagen Induction Mouse Models for Pharmacological Evaluation of Anti-Androgenic Agents

Background and objectives: Androgen-induced hair loss and anagen induction mouse models are commonly used in Androgenetic alopecia (AGA) studies. This paper aims to verify the feasibility of these models for evaluating the androgen receptor (AR) antagonist in vivo and investigated its pharmacological mechanism via biomarker study. Methods: We compared various doses and administration routes of dihydrotestosterone (DHT) and testosterone propionate (TP) to optimize the androgen-induced hair loss model. The efficacy of Minoxidil and Pyrilutamide (KX-826, Kintor Pharma, Suzhou China) was evaluated using the optimized androgen-induced hair loss model and the anagen induction mouse model. We investigated the pharmacological mechanism of Pyrilutamide via biomarker studies. Results: Subcutaneous administration of 30 mg/kg of DHT slowed hair growth, and no apparent skin lesions were observed, making it the optimal dose for efficacy experiments. Both Minoxidil and Pyrilutamide significantly promoted hair growth in androgen-induced hair loss and the anagen induction mouse models. Minoxidil and Pyrilutamide both decreased the AR protein level and enhanced the Wnt/β-Catenin signaling pathway. Conclusions: The anagen induction mouse model and the optimized androgen-induced hair loss model are suitable for evaluating anti-androgenic agents. These models can be used to study the efficacy and pharmacological mechanisms of novel AGA treatments.