Evidence that 1,25-dihydroxyvitamin D3 is the physiologically active metabolite of vitamin D3.

I. Introduction THE REALIZATION in the mid-1960s that vitamin D3 is metabolized led to an extensive effort by several laboratories to identify the metabolites produced and determine their biological activities. The identification of 1,25-dihydroxyvitamin D3 [1,25-(OH)2D3] as the most potent and rapidly acting metabolite of vitamin D3 in stimulating intestinal absorption of calcium and mobilization of bone mineral suggested that this compound is the physiologically active hormonal form of the vitamin. Subsequent studies showing the rapid biological turnover of 1,25-(OH)2D3, the presence of a specific 1,25-(OH)2D3 receptor in target tissues, and the intricate regulation of the renal 25-hydroxyvitamin D3 (25-OHD3)-1-hydroxylase all supported this theory. However, by the late 1970s the possibility that additional metabolites of vitamin D3 have actions distinct from those of 1,25-(OH)2D3, particularly on skeletal mineralization and embryonic chick development, was suggested by several groups. Particular attent...