Sustained osteoblast nuclear receptor binding of converted 1alpha, 25-dihydroxyvitamin D3 after administration of 3H-1alpha-hydroxyvitamin D3: a combined receptor autoradiography and radioassay time course study with comparison to 3H-1alpha, 25-dihydroxyvitamin D3.

The present study was undertaken to clarify the receptor distribution and the pharmacokinetics of 3H-1alpha(OH)D3, and 3H-1alpha,25(OH)2D3 for comparison. Receptor autoradiography was used after intravenous injection to 3-day-old neonatal rats and radioassay-HPLC after oral application to young adult rats. Corresponding results were obtained from both receptor autoradiography and radioassay. After 3H-1alpha(OH)D3 administration, uptake was delayed but sustained over a long period of time and the concentration of silver grains (autoradiography) or recovered 3H-1alpha,25(OH)2D3 (radioassay) peaked at a lower level. After 3H-1alpha,25(OH)2D3 administration, osteoblast nuclear, whole bone uptake and retention of radiolabeled compound were relatively rapid and short in duration. Nuclear uptake in osteoblasts after administration of 3H-1alpha(OH)D3 was abolished in competition studies with 10-fold unlabeled 1alpha,25(OH)2D3. These results indicate that 1alpha(OH)D3 continuously supplies osteoblasts with converted 1alpha,25(OH)2D3 and would not spread to the cells because of the low binding affinity of the receptor. Accordingly, 1alpha(OH)D3 appears to have some therapeutic properties different from 1alpha,25(OH)2D3 because of a relatively slow and sustained accumulation of the receptor and less Cmax (pharmacokinetics) compared with 1alpha,25(OH)2D3.