Newly Recognized Receptors for Vitamin D Metabolites

Vitamin D plays a central role in modulating calcium and phosphate homeostasis in the body. While the effects of its principal stimulatory metabolite, 1,25(OH)2D3, have been studied extensively in many physiological and disease states, research results have now emerged suggesting the possible biological role for another metabolite, 24,25(OH)2D3. The actions of 1,25(OH)2D3 are believed to be mediated by both pregenomic and genomic pathways involving the classical vitamin D receptor (VDR) and the more recently identified 1,25D3-MARRS (Membrane associated, rapid response steroid binding) receptor, also known as PDIA3/ERp57/GRp58/ERp60/ERp61. The metabolite 24,25(OH)2D3 is made when an animal is vitamin D replete and provides an endocrine feedback loop to inhibit the rapid actions of 1,25(OH)2D3, which appear to be mediated by 24,25(OH)2D3 binding to a subset of catalase at the plasma membrane. Here we discuss these two recently identified putative receptors for vitamin D metabolites while also reviewing 25(OH)D3 as a functional metabolite.