INSULIN MARKEDLY POTENTIATES THE CAPACITY OF PARATHYROID-HORMONE TO INCREASE EXPRESSION OF 25-HYDROXYVITAMIN D-3-24-HYDROXYLASE IN RAT OSTEOBLASTIC CELLS IN THE PRESENCE OF 1,25-DIHYDROXYVITAMIN D-3

We have previously shown that insulin alters the renal metabolism of 2 5-hydroxyvitamin D, To examine the effect of insulin on vitamin D meta bolism in bone, we have used UMR-106 osteoblast-like cells to study th e regulation of 25(OH)D-3-24-hydroxylase (24-hydroxylase) expression b y insulin. The 24-hydroxylase is an important enzyme in degrading 1,25 -dihydroxyvitamin D-3 (1,25(OH)(2)D) in target tissues, Insulin alone had no effect on mRNA levels of the cytochrome P450 component (CYP24) of the 24-hydroxylase or on 24-hydroxylase activity itself in UMR cell s. However, insulin increased the capacity of parathyroid hormone (PTH ) to elevate CYP24 mRNA levels by 3-4-fold and to increase 24-hydroxyl ase activity by 2-fold in the presence of 1,25(OH)(2)D, Insulin increa sed the maximal responsiveness of UMR cells to PTH without altering th eir sensitivity, The action of insulin required the presence of 1,25(O H)(2)D and was partly dependent on new protein synthesis, Insulin-like growth factor 1 also potentiated the effects of PTH, This marked stim ulation of the 24-hydroxylase by PTH and insulin may serve to regulate 1,25(OH)(2)D action and/or to produce 24,25-dihydroxyvitamin D in bon e cells.