Effects of glucocorticoid on signalling by prostaglandin E 2 in osteoblast-like cells

Abstract

It is well-known that osteoporosis is a common complication of patients with glucocorticoid excess. We previously reported that dexamethasone inhibits Ca 2+ influx induced by prostaglandin E 2 (PGE 2), a potent bone resorbing agent, in osteoblast-like MC3T3-E1 cells (O. Kozawa, H. Tokuda, J. Kotoyori, A. Suzuki, Y. Ito and Y. Oiso, Prostagland Leuk Essent Fatty Acids, in press). In the present study, we examined the effects of dexamethasone on cyclic adenosine monophosphate (cAMP) accumulation and phosphoinositide hydrolysis by PGE 2 in MC3T3-E1 cells. The pretreatment with dexamethasone significantly inhibited cAMP accumulation stimulated by PGE 2 in a dose-dependent manner in the range between 10 pM and 1 nM in MC3T3-E1 cells. This effect of dexamethasone was dependent on the time of pretreatment up to 8 h. Dexamethasone also inhibited the cAMP accumulation induced by NaF, an activator of guanosine triphosphate (GTP)-binding protein, or forskolin which directly activates adenylate cyclase. In contrast, dexamethasone had little effect on the formation of inositol phosphates stimulated by PGE 2 in MC3T3-E1 cells. These results strongly suggest that glucocorticoid modulates the signal transduction by PGE 2 in osteoblast-like cells and that it inhibits PGE 2-induced cAMP production without affecting PGE 2-induced phosphoinositide hydrolysis.