Vitamin D and intestinal calcium absorption

Abstract

The principal function of vitamin D in calcium homeostasis is to increase calcium absorption from the intestine. Calcium is absorbed by both an active transcellular pathway, which is energy dependent, and by a passive paracellular pathway through tight junctions. 1,25Dihydroxyvitamin D(3) (1,25(OH)(2)D(3)) the hormonally active form of vitamin D, through its genomic actions, is the major stimulator of active intestinal calcium absorption which involves calcium influx, translocation of calcium through the interior of the enterocyte and basolateral extrusion of calcium by the intestinal plasma membrane pump. This article reviews recent studies that have challenged the traditional model of vitamin D mediated transcellular calcium absorption and the crucial role of specific calcium transport proteins in intestinal calcium absorption. There is also increasing evidence that 1,25(OH)(2)D(3) can enhance paracellular calcium diffusion. The influence of estrogen, prolactin, glucocorticoids and aging on intestinal calcium absorption and the role of the distal intestine in vitamin D mediated intestinal calcium absorption are also discussed.

Figure 1

Models of vitamin D mediated intestinal calcium absorption. Left panel: Transcellular intestinal calcium absorption. 1,25(OH)₂D₃, through its genomic actions, stimulates active intestinal calcium absorption. The traditional model of transcellular calcium transport involves calcium influx through TRPV6, intracellular calcium transfer by calbindin (CaBP) and calcium extrusion by the plasma membrane calcium ATPase (Ca pump). Recent studies using KO mice have suggested that TRPV6 and calbindin are not critical for 1,25(OH)₂D₃ calcium absorption and maybe compensated by another channel or protein. Right panel: Paracellular pathway. There is increasing evidence that 1,25(OH)₂D₃ can enhance paracellular calcium diffusion by regulating tight junction proteins. (Reproduced with permission from Wasserman RH, 2005).