VITAMIN D AND CALCIUM TRANSPORT *

Perhaps the most significant single factor involved in utilization of calcium from the environment and its regulation in extracellular fluid is vitamin D. In 1928 Orr and his collaborators1 first noted the excessive loss of calcium in the feces of animals deprived of vitamin D. They concluded correctly that vitamin D stimulates intestinal absorption of calcium. This initial discovery was ignored and criticized until the definitive work of Nicolaysen in the 1930s,'J which established clearly the role of vitamin D in initiating intestinal calcium absorption. In addition t o these discoveries. i t is now well known that vitamin D participates in the transfer of calcium across a number of membranes, although the best and most studied is that of the intestine. FIGURE I illustrates the sites of vitamin D function in calcium transfer reactions bringing about the elevation of plasma calcium concentration that prevents hypocalcemic tetany or convulsions on one hand and provides sufficient amounts of calcium to satisfy the mineralization of bone on the other. It is well known that calcium is held constantly at a value of about 10 mg per 100 ml and in response to hypocalcemia. the parathyroid glands secrete parathyroid hormone which functions directly in the mobilization of calcium from bone4 and in renal reabsorption of calcium. This hormone also functions to stimulate the metabolism of vitamin D to its active hormone, 1,2S-dihydroxyvitamin D3 (1,25-(OH), D:,)'..J,6 This substance then stimulates intestinal calcium a b ~ o r p t i o n . ~ the transfer of calcium from the bone fluid compartment to the extracellular fluid compartment? and renal calcium reabsorption in the distal convoluted tubule of the kidney.g In the latter two functions parathyroid hormone and the active form of vitamin D apparently work hand in hand being interdependent on each other.4 I n addition to these calcium transport systems, it is also known that vitamin D plays an important role in the transfer of calcium in the shell gland of birds at the time of egg shell formation.'" Of a11 of these calcium transfer systems, the only one that has been studied in any detail is that found in the intestinal mucosal cells. Therefore, the remarks presented here will deal primarily with this calcium transport system. TABLE 1 provides some basic information regarding the intestinal calcium transport system which has been investigated over the past 25 years. Following