Mechanism of action of 1,25-dihydroxyvitamin D3 on intestinal calcium absorption

Abstract

1,25-Dihydroxyvitamin D₃ (1,25(OH)₂D₃) is the major controlling hormone of intestinal calcium absorption. As the body’s demand for calcium increases from a diet deficient in calcium, from growth, pregnancy or lactation, the synthesis of 1,25(OH)₂D₃ is increased resulting in the stimulation of intestinal calcium absorption. However a complete description of the molecular mechanisms involved in the 1,25(OH)₂D₃ regulated calcium absorptive process remains incomplete. Intestinal calcium absorption occurs by both an active saturable transcellular pathway and a passive nonsaturable paracellular pathway. Each step in the process of transcellular calcium transport (apical entry of calcium, translocation of calcium through the interior of the enterocyte and basolateral extrusion of calcium by the plasma membrane pump) has been reported to involve a vitamin D dependent component. This article will review recent studies, including those using knockout mice, that have suggested that 1,25(OH)₂D₃ mediated calcium absorption is more complex than the traditional three step model of transcellular calcium transport. Current concepts are reviewed and questions that remain are addressed. Evidence for a role of 1,25(OH)₂D₃ in the regulation of the paracellular pathway is also discussed.