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

The study explored the role of the vitamin D receptor (VDR) in maintaining hair follicle homeostasis, particularly in the context of alopecia associated with VDR mutations in humans and VDR null mice. It was found that alopecia resulted from an inability to initiate the anagen phase of the hair cycle after follicle morphogenesis. The research demonstrated that VDR expression in keratinocytes is crucial for hair cycle maintenance. By targeting mutant VDR transgenes to keratinocytes in VDR null mice, it was shown 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, affecting nuclear receptor coactivator recruitment, only partially rescued hair cycling. The study concluded that the effects of VDR on hair follicles were ligand-independent, highlighting novel molecular and cellular actions of this nuclear receptor.