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-dihydroxyv itamin D-3 (1,25(OH)(2)D-3), 17 beta-estradiol, or dexamethasone on [1 -C-14]arachidonic acid (AA) uptake and distribution into glycerophosph olipid classes by normal adult human osteoblast-like (hOB) cells were investigated. Total uptake of [1-C-14]AA was decreased in cells treate d with dexamethasone when assayed after a 24-, 48-, or 96-h exposure t o the hormone. Specific radiolabel incorporation into phosphatidylchol ine was reduced by a 48-h treatment with dexamethasone with a concurre nt 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 o f [1-C-14]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 decrea se in the proportional radiolabeling of the phosphatidylinositol pool was identified (92 +/- 2% of control, P < 0.05). The 1,25(OH)(2)D-3-de pendent decrease in total uptake and in phosphatidylinositol incorpora tion of [1-C-14]AA were found to be hormone dose dependent. Treatment with 24,25(OH)(2)D-3 was without effect on either total [1-C-14]AA upt ake or the specific [1-C-14]AA radiolabeling of the phosphatidylinosit ol pool. 1,25(OH)(2)D-3 treatment decreased hOB fell uptake of [1-C-14 ]oleic acid and decreased its proportional incorporation into the phos phatidylinositol pool. Gas chromatographic analyses revealed no 1,25(O H)(2)D-3-dependent effects on total phosphatidylinositol lipid mass or on the mole percent of arachidonic acid within the phosphatidylinosit ol pool, leaving the mechanism of the effects of the secosteroid on hO B cell AA metabolism unexplained. 17 beta-Estradiol had no effects on the parameters of AA metabolism measured. As a consequence of their mo dulation of arachidonic acid uptake and its distribution into hOB cell ular phospholipids, steroids might alter the biological effects of oth er hormones whose actions include the stimulated production of bioacti ve AA metabolites, such as prostaglandins or the various lipoxygenase products. (C) 1995 Wiley-Liss, Inc.