Effect of dexamethasone on 25-hydroxyvitamin D3 metabolism by chick kidney cell cultures

The ability of dexamethasone to alter the metabolism of [3H]25-hydroxyvitamin D3 ([3H]25OHD3) metabolism by primary cultures of chick kidney cells was tested. Dexamethasone, present for 24 or 48 h at 10(-8)-10(-6) M, decreased production of [3H]1,25-dihydroxyvitamin D3 to approximately 60% of control levels. If cultures were pretreated with 1,25-dihydroxyvitamin D3 to reduce 25OHD3-1-hydroxylase activity and induce 25OHD3-24-hydroxylase activity, no effect of dexamethasone on either of the enzymes was observed. When the substrate concentration was varied, analysis of the data revealed that dexamethasone decreases both the maximal velocity of the rate of 1-hydroxylation to 25OHD3 and the half-maximal substrate concentration for 25OHD3. Dexamethasone had no effect on the cell number of the cultures, as assessed by DNA content, but did reduce the total protein content to approximately 70% of control values. Dexamethasone did not alter the response of chick kidney cells to PTH in terms of cAMP production or the metabolism of 25OHD3. The results suggest that dexamethasone has the potential to alter 25OHD3 metabolism through a direct effect on the renal cell.