PARATHYROID-HORMONE AND 1,25-DIHYDROXYVITAMIN-D SYNERGISTICALLY INDUCE THE 1,25-DIHYDROXYVITAMIN-D 24-HYDROXYLASE IN RAT UMR-106 OSTEOBLAST-LIKE CELLS

We have studied the effect of parathyroid hormone (PTH) and 1,25-dihydroxyvitamin D-3 (1,25(OH)(2)D) on the expression of the 1,25-dihydroxyvitamin D-24-hydroxylase (24-hydroxylase) in rat UMR-106 osteoblastic cells. 1,25(OH)(2)D (10(-7) M) alone produced a gradual increase in mRNA levels of the 24-hydroxylase cytochrome P450 component (P450cc24) during 12 hours of incubation. Rat PTH 1-34 (250 nM) in the presence of 1,25(OH)(2)D further increased P450cc24 mRNA levels 7-10 fold after 3 hours. PTH alone had no significant effect. The action of PTH was mimicked by forskolin but not by phorbol ester. The 24-hydroxylase enzymatic activity in UMR cells was increased over 5-fold by PTH and 1,25(OH)(2)D together compared to 1,25(OH)(2)D alone after 6 hours. This synergistic regulation of the 24-hydroxylase in bone cells is in contrast to the regulation in the kidney, where PTH and 1,25(OH)(2)D have opposite effects on 24-hydroxylase expression. (C) 1994 Academic Press, Inc.