EC Nutrition

In a previous paper, we addressed several important issues concerning the actual physiological behavior of vitamin D (Vit D), focusing not only on its metabolism but, more importantly, on its biological effects in the numerous extrarenal cells capable of expressing either the Vit D receptor (VDR) or the enzyme CYP27B1. We also highlighted several unresolved questions regarding the relative contribution of renal calcitriol production compared with that generated within extrarenal tissues, as well as the molecular mechanisms regulating CYP27B1 expression. Despite the considerable advances in our understanding of calcitriol biology, many questions still require further clarification. Among these, particular attention should be paid to the mechanisms regulating the entry of 25-hydroxyvitamin D (25OHD) into extrarenal cells, its subsequent intracellular fate, the optimal concentrations required for biological activity, and the mechanisms underlying its depletion.

Keywords: Vitamin D Metabolism; Vitamin D Receptor; CYP27B1 Expression; Extrarenal Tissues; DBP; Megalin-Cubilin

1. Daniel D Bikle. “Vitamin D metabolism, mechanism of action, and clinical applications”. Chemistry and Biology 3 (2014): 319-329.
2. Daniel D Bikle., et al. “Vitamin D: Production, metabolism, and mechanism of action”. In: Endotext [Internet]. South Dartmouth (MA): MDText.com, Inc. (2000).
3. Kaseda R., et al. “Role of megalin and cubilin in the metabolism of vitamin D(3)”. Therapeutic Apheresis and Dialysis 1 (2011): 14-17.
4. Adams JS., et al. “Redefining human vitamin D sufficiency: back to the basics”. Bone Research 1 (2013): 2-10.
5. Chun RF., et al. “Vitamin D and DBP: the free hormone hypothesis revisited”. Journal of Steroid Biochemistry and Molecular Biology A (2014): 132-137.
6. Adams JS., et al. “Regulation of the extrarenal CYP27B1-hydroxylase”. Journal of Steroid Biochemistry and Molecular Biology A (2014): 22-27.
7. Nowacka A., et al. “CYP24A1 in small intestinal vitamin D metabolism and clinical implications”. Nutrients 21 (2025): 3348.