EFFECTS OF GLUCOCORTICOID ON SIGNALING BY PROSTAGLANDIN-E(2) IN OSTEOBLAST-LIKE CELLS

It is well-known that osteoporosis is a common complication of patient s with glucocorticoid excess. We previously reported that dexamethason e inhibits Ca2+ influx induced by prostaglandin E2 (PGE2), a potent bo ne resorbing agent, in osteoblast-like MC3T3-E1 cells (0. Kozawa, H. T okuda, J. Kotoyori, A. Suzuki, Y. Ito and Y. Oiso, Prostagland Leuk Es sent Fatty Acids, in press). In the present study, we examined the eff ects of dexamethasone on cyclic adenosine monophosphate (cAMP) accumul ation and phosphoinositide hydrolysis by PGE2 in MC3T3-E1 cells. The p retreatment with dexamethasone significantly inhibited cAMP accumulati on stimulated by PGE2 in a dose-dependent manner in the range between 10 pM and 1 nM in MC3T3-E1 cells. This effect of dexamethasone was dep endent on the time of pretreatment up to 8h. Dexamethasone also inhibi ted the cAMP accumulation induced by NaF, an activator of guanosine tr iphosphate (GTP)-binding protein, or forskolin which directly activate s adenylate cyclase. In contrast, dexamethasone had little effect on t he formation of inositol phosphates stimulated by PGE2 in MC3T3-E1 cel ls. These results strongly suggest that glucocorticoid modulates the s ignal transduction by PGE2 in osteoblast-like cells and that it inhibi ts PGE2-induced cAMP production without affecting PGE2-induced phospho inositide hydrolysis.