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

Abstract.

The present study was undertaken to clarify the receptor distribution and the pharmacokinetics of ³H-1α(OH)D₃, and ³H-1α,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-1α(OH)D₃ administration, uptake was delayed but sustained over a long period of time and the concentration of silver grains (autoradiography) or recovered ³H-1α,25(OH)₂D₃ (radioassay) peaked at a lower level. After ³H-1α,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-1α(OH)D₃ was abolished in competition studies with 10-fold unlabeled 1α,25(OH)₂D₃. These results indicate that 1α(OH)D₃ continuously supplies osteoblasts with converted 1α,25(OH)₂D₃ and would not spread to the cells because of the low binding affinity of the receptor. Accordingly, 1α(OH)D₃ appears to have some therapeutic properties different from 1α,25(OH)₂D₃ because of a relatively slow and sustained accumulation of the receptor and less C_max (pharmacokinetics) compared with 1α,25(OH)₂D₃.