Vitamin D Metabolism and Function in the Skin

The study demonstrated that both the vitamin D receptor (VDR) and hairless (Hr) genes were crucial for the mammalian hair cycle, as mutations in either led to total alopecia. VDR functioned as a ligand-activated transcription factor, while Hr acted as a corepressor. The research showed that Hr significantly inhibited VDR-mediated transactivation, affecting both synthetic and natural VDR-responsive promoters. Hr was found to bind directly to VDR, suggesting an in vivo interaction, with the Hr contact site in VDR located in the ligand binding domain. Coimmunoprecipitation and functional studies indicated that VDR interacted with a C-terminal region of Hr. In situ hybridization in mouse skin showed colocalization of hr and VDR mRNAs in hair follicle cells, supporting the hypothesis of an intracellular interaction to repress VDR target gene expression.

The study investigated the effects of normalizing mineral ion levels through diet in vitamin D receptor (VDR)-ablated mice. It was found that this dietary intervention prevented secondary hyperparathyroidism, rickets, and osteomalacia by normalizing growth and serum ionized calcium levels. Despite these improvements, alopecia persisted in the VDR-ablated mice, indicating that the vitamin D receptor is essential for normal hair growth. This suggested that while mineral ion homeostasis could prevent certain bone-related conditions, it did not address hair loss associated with VDR deficiency.