Expression of transcellular and paracellular calcium and magnesium transport proteins in renal and intestinal epithelia during lactation.

Significant alterations in maternal calcium (Ca) and magnesium (Mg) balance occur during lactation. Ca is the primary divalent cation mobilized into breast milk by demineralization of the skeleton and alterations in intestinal and renal Ca transport. Mg is also concentrated in breast milk, but the underlying mechanisms are not well understood. To determine the molecular alterations in Ca and Mg transport in the intestine and kidney during lactation, three groups of female mice consisting of either nonpregnant controls, lactating mice, or mice undergoing involution were examined. The fractional excretion of Ca, but not Mg, rose significantly during lactation. Renal 1-α hydroxylase and 24-OHase mRNA levels increased markedly, as did plasma 1,25 dihydroxyvitamin D levels. This was accompanied by significant increases in intestinal expression of and in lactating mice. However, no alterations in the expression of cation-permeable claudin-2, claudin-12, or claudins-15 were found in the intestine. In the kidney, increased expression of and was observed during lactation, while no changes in claudins involved in Ca and Mg transport (claudin-2, claudin-14, claudin-16, or claudin-19) were found. Consistent with the mRNA expression, expression of both calbindin-D and transient receptor potential vanilloid 5 (TRPV5) proteins increased. Colonic expression increased during lactation, while renal remained unaltered. In conclusion, proteins involved in transcellular Ca and Mg transport pathways increase during lactation, while expression of paracellular transport proteins remained unchanged. Increased fractional Ca excretion can be explained by vitamin D-dependent intestinal hyperabsorption and bone demineralization, despite enhanced transcellular Ca uptake by the kidney.