The endocrinology of vitamin D. The left panel depicts the essentials of the endocrine synthesis, metabolism and action of vitamin D. The key enzyme in the synthesis of the active, vitamin D receptor-(VDR) interacting metabolite, 1,25-dihydroxyvitamin D, is the CYP27b1-hydroxylase. In normal, human endocrine physiology the CYP27b1-hydroxylase is expressed principally in the kidney but also in the placenta. The catabolic CYP24a1-24-hydroxylase is ubiquitously distributed among human tissues and serves to inactivate 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D. The right panel shows the endocrine responses of the vitamin D pathway to a hypocalcemic challenge and the human host’s use of the skeleton to restore blood calcium levels back to normal. Abbreviations include: CaSR, calcium sensing receptor; PTH, parathyroid hormone; PTH/PTHrP, receptor for PTH and parathyroid hormone-related protein; DBP, serum vitamin D binding protein; RXR, retinoid X receptor; VDRE, vitamin D response element; Ca++, calcium ion; PO4--, phosphate ion; RANKL, receptor activator of nuclear factor kappa-B ligand; FGF23, fibroblast growth factor-23. Figure adapted with the permission of the original authors.