Calcitriol (1,25-dihydroxyvitamin D₃)

Synthesis involves three organs. In the skin, ultraviolet B light (≈290–315 nm) converts 7-dehydrocholesterol to previtamin D₃, which isomerises to cholecalciferol (vitamin D₃); vitamin D₂ (ergocalciferol) and D₃ also come from the diet. In the liver, 25-hydroxylase (CYP2R1) forms 25-hydroxyvitamin D (calcidiol) — the main circulating and storage form, with a half-life of 2–3 weeks, measured to assess vitamin D status. In the proximal tubule of the kidney, 1α-hydroxylase (CYP27B1) forms 1,25-dihydroxyvitamin D (calcitriol); this step is tightly regulated and is the true endocrine control point.

Calcitriol travels on vitamin D-binding protein and acts on the nuclear vitamin D receptor (VDR), a transcription factor heterodimerising with RXR. In the duodenum it induces the apical Ca²⁺ channel TRPV6, the cytosolic carrier calbindin-D9k and the basolateral Ca²⁺-ATPase, and increases phosphate absorption. In bone it provides the minerals for mineralisation and, at high levels, promotes osteoclast activation via RANKL; in the kidney it enhances distal Ca²⁺ reabsorption; in the parathyroid it suppresses PTH transcription.