REGULATION OF THE TRANSCRIPTION OF PARATHYROID-HORMONE PARATHYROID-HORMONE-RELATED PEPTIDE RECEPTOR MESSENGER-RNA BY DEXAMETHASONE IN ROS-17/2.8 OSTEOSARCOMA CELLS/

Previous studies have shown that dexamethasone enhanced the expression of parathyroid-hormone/parathyroid-hormone-related peptide (PTH/PTHrP ) receptor mRNA in ROS 17/2.8 osteosarcoma cells. The aim of this stud y was to determine whether the induction of PTH/PTHrP receptor express ion in such osteoblast-like cells is regulated at the gene level. Dexa methasone increased the steady-state levels of PTH/PTHrP receptor mRNA twofold at 6 h, and nearly threefold at 24 h. The half-life of the PT H/PTHrP receptor mRNA, in the presence of actinomycin D, was 6 h both in untreated and in dexamethasone-treated cells. When measured by nucl ear run-on assay, the rate of PTH/PTHrP receptor gene transcription wa s increased twofold at 24 h. PTH/PTHrP receptor mRNA expression was bl ocked completely after 24 h of treatment with cycloheximide. The bindi ng of PTH/PTHrP to their receptor required the synthesis of new protei n and was shown to be specifically dependent on the interaction of dex amethasone with the glucocorticoid receptor. These data indicate that the enhancing effect of dexamethasone on PTH/PTHrP receptor expression is rapid, requires de novo protein synthesis, and increases the trans cription rate of the PTH/PTHrP receptor gene.