Biological activity assessment of 1 alpha,25-dihydroxyvitamin D3-26,23-lactone in the rat.

1 alpha,25-Dihydroxyvitamin D3-26,23-lactone [1 alpha,25(OH)2D3-26,23-lactone] was compared to 1 alpha,25-dihydroxyvitamin D3 [1 alpha,25(OH)2D3] in terms of their stimulation, in vivo, of intestinal calcium transport and mobilization of calcium from bone in the rat (the two classic vitamin D-mediated responses), and their relative binding to the chick intestinal receptor for 1 alpha,25(OH)2D3, 1 alpha,25-(OH)2D3-26,23-lactone was found to be only one-thirtieth as active as 1 alpha,25-(OH)2D3 in the stimulation of intestinal calcium transport and was found to mediate a significant reduction in the steady-state serum calcium levels. Associated with the reduction in serum calcium was a significant increase in urinary calcium excretion for 24 h after the administration of the steroid. Prior administration of 1 alpha,25(OH)2D3-26,23-lactone partially blocked the actions of a subsequently administered dose of 1 alpha,25(OH)2D3 in increasing serum calcium levels, but did not affect the action of 1 alpha,25(OH)2D3 in stimulating intestinal calcium transport. The binding affinity of 1 alpha,25(OH)2D3-26,23-lactone to the chick intestinal cytosol receptor protein was observed to be 670 times lower than that of 1,25-(OH)2D3 which indicates that perturbation of the 25-hydroxylated side chain by formation of the 26,23-lactone causes a significant reduction in ligand affinity for the receptor.