Therapeutic potential of isoproterenol in androgenetic alopecia: activation of hair follicle stem cells via the PI3K/AKT/β-Catenin signaling pathway.

Background: Androgenetic alopecia (AGA) is characterized by the depletion or dormancy of hair follicle stem cells (HFSCs), leading to hair thinning and miniaturization. Reactivating the dormant HFSCs is a promising therapeutic approach. Adrenergic β2 receptor (ADRB2) activation has been shown to promote hair growth in animal models via the Sonic Hedgehog (SHH) pathway, but its potential for treating clinical AGA patients remains unexamined.

Methods: We investigated the role of the PI3K/AKT signaling pathway in AGA pathogenesis, focusing on the hair follicle-sympathetic nerve axis. The ADRB2 agonist, isoproterenol (ISO), was administered to assess its effects on AGA hair follicle organ culture model and HFSC proliferation. The mechanisms underlying these effects were explored by analyzing the PI3K/AKT/β-Catenin pathway.

Results: Our results showed abnormal PI3K/AKT pathway expression in AGA hair follicles, with associated defects in the hair follicle-sympathetic nerve axis. ISO treatment accelerated AGA hair follicle growth and promoted the proliferation of HFSC. Mechanistically, ISO facilitated the HFSC activation by modulating the PI3K/AKT/β-Catenin pathway.

Conclusions: ISO effectively promotes hair growth in both animal models and AGA patients. ISO stimulating the proliferation of dormant cell population enriched in HFSC. This process was likely mediated by the PI3K/AKT/β-Catenin pathway. These findings provide novel insights into the reactivation of HFSCs and suggest that adrenergic signaling stimulation may be a promising strategy for managing hair loss.