1,25‐Dihydroxyvitamin D 3 or dexamethasone modulate arachidonic acid uptake and distribution into glycerophospholipids by normal adult human osteoblast‐like cells

The effects of treatment with the osteotropic steroids 1,25‐dihydroxyvitamin D 3 (1,25(OH) 2 D 3 ), 17β‐estradiol, or dexamethasone on [1‐ 14 C]arachidonic acid (AA) uptake and distribution into glycerophospholipid classes by normal adult human osteoblast‐like (hOB) cells were investigated. Total uptake of [1‐ 14 C]AA was decreased in cells treated with dexamethasone when assayed after a 24‐, 48‐, or 96‐h exposure to the hormone. Specific radiolabel incorporation into phosphatidylcholine was reduced by a 48‐h treatment with dexamethasone with a concurrent increase in the radiolabeling of phosphatidylethanolamine. However, these changes were transient, and by 96 h of dexamethasone treatment the distribution of the radiolabeled fatty acid had reequilibrated to resemble the pattern found for vehicle treated samples. Total uptake of [1‐ 14 C]AA was diminished by 96‐h treatment with 1,25(OH) 2 D 3 (79 ± 3% of control, P < 0.01); at that time point, a significant decrease in the proportional radiolabeling of the phosphatidylinositol pool was identified (92 ± 2% of control, P < 0.05). The 1,25(OH) 2 D 3 ‐dependent decrease in total uptake and in phosphatidylinositol incorporation of [1‐ 14 C]AA were found to be hormone dose dependent. Treatment with 24,25(OH) 2 D 3 was without effect on either total [1‐ 14 C]AA uptake or the specific [1‐ 14 C]AA radiolabeling of the phosphatidylinositol pool. 1,25(OH) 2 D 3 treatment decreased hOB cell uptake of [1‐ 14 C]oleic acid and decreased its proportional incorporation into the phosphatidylinositol pool. Gas chromatographic analyses revealed no 1,25(OH) 2 D 3 ‐dependent effects on total phosphatidylinositol lipid mass or on the mole percent of arachidonic acid within the phosphatidylinositol pool, leaving the mechanism of the effects of the secosteroid on hOB cell AA metabolism unexplained. 17β‐Estradiol had no effects on the parameters of AA metabolism measured. As a consequence of their modulation of arachidonic acid uptake and its distribution into hOB cellular phospholipids, steroids might alter the biological effects of other hormones whose actions include the stimulated production of bioactive AA metabolites, such as prostaglandins or the various lipoxygenase products.