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

The present study was undertaken to clarify the receptor distribution and the pharmacokinetics of H-3-1 alpha(OH)D-3, and H-3-1 alpha,25(OH)(2)D-3 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 H-3-1 alpha(OH)D-3 administration, uptake was delayed but sustained over a long period of time and the concentration of silver grains (autoradiography) or recovered H-3-1 alpha,25(OH)(2)D-3 (radioassay) peaked at a lower level. After H-3-1 alpha,25(OH)(2)D-3 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 H-3-1 alpha(OH)D-3 was abolished in competition studies with 10-fold unlabeled 1 alpha,25(OH)(2)D-3. These results indicate that 1 alpha(OH)D-3 continuously supplies osteoblasts with converted 1 alpha,25(OH)(2)D-3 and would not spread to the cells because of the low binding affinity of the receptor. Accordingly, 1 alpha(OH)D-3 appears to have some therapeutic properties different from 1 alpha,25(OH)(2)D-3 because of a relatively slow and sustained accumulation of the receptor and less C-max (pharmacokinetics) compared with 1 alpha,25(OH)(2)D-3.