In osteoblast-like MC3T3-E1 cells, eve previously reported that prostaglandin E(2) (PGE(2)), a potent bone resorbing agent, stimulates Ca2+ influx (H. Tokuda, M. Miwa, Y. Oiso and O. Kozawa, Cell Signal 1992; 4: 261-266). In this study, we examined the effects of various hormones belonging to the steroid hormone superfamily on PGE(2) -induced Ca2+ influx in MC3T-E1 cells. 1,25-Dihydroxyvitamin D-3 [1,25-(OH)(2)D-3], an active form of vitamin D-3, dexamethasone and retinoic acid significantly inhibited the PGE(2)-induced Ca2+ influx in a dose-dependent manner in these cells. The effects of these hormones were dependent on the time of pretreatment and submaximum inhibitions were observed at 6 h. In contrast, 24,25-dihydroxyvitamin D-3 [24,25-(OH)(2)D-3], an inactive form of vitamin D-3, 17 beta-estradiol, progesterone, testosterone and triiodothyronine had little effect on the PGE(2)-induced Ca2+ influx in these cells. These results suggest that, in the steroid hormone superfamily, 1,25-dihydroxyvitamin D-3, glucocorticoid and retinoic acid modulate bone metabolism through the inhibition of Ca2+ influx induced by PGE(2) in osteoblast-like cells.