Ligand-Independent Actions of the Vitamin D Receptor Maintain Hair Follicle Homeostasis

This study explored the role of the vitamin D receptor (VDR) in hair follicle homeostasis, particularly its ligand-independent actions. Alopecia in humans and VDR null mice was linked to the inability to initiate the anagen phase of the hair cycle. The research demonstrated that VDR expression in keratinocytes is crucial for maintaining the hair cycle. By using mutant VDR transgenes in VDR null mice, it was found that a mutation in the hormone-binding domain, which prevents ligand binding, could restore normal hair cycling. In contrast, a mutation in the activation function 2 domain only partially rescued hair cycling. The study also noted that mutations in the nuclear receptor corepressor Hairless, which interacts with VDR, are associated with alopecia, but VDR mutations did not affect Hairless interactions. These findings highlighted the ligand-independent effects of VDR on hair follicles and suggested new molecular and cellular functions of this receptor.