Differential effects of glucocorticoids on bone resorption in neonatal mouse calvariae stimulated by peptide and steroid-like hormones

Differential effects on in vitro bone resorption were observed when the glucocorticoids, hydrocortisone and dexamethasone, were added to neonatal mouse calvariae treated with either parathyroid hormone (PTH), 1,25(OH)(2)-vitamin D-3, all trans-retinoic acid (t-RA), or prostaglandin E-2 (PGE(2)). Bone resorption was assessed by analyzing either the release of Ca-45 from [Ca-45]CaCl2 prelabeled calvarial bones or the release of H-3 from [H-3]proline prelabeled calvariae. At PGE(2) concentrations of 3 x 10(-8) and 3 x 10(-7) mol/l, co-treatment with either 10(-6) mol/l dexamethasone or 10(-6) mol/l hydrocortisone caused additive Ca-45 release from neonatal mouse calvariae. In contrast, synergistic release from mouse calvarial bones of both Ca-45 and H-3 was found after either 10(-6) mol/l hydrocortisone or 10(-6) mol/l dexamethasone was combined with 3 x 10(-11) mol/l PTH treatment for 120 h. Dose-response studies indicated that the synergistic stimulation of Ca-45 release from neonatal mouse calvariae by glucocorticoids and PTH could be elicited at glucocorticoid concentrations of 10(-8) to 10(-6) mol/l and at PTH concentrations of 10(-11) to 10(-9) mol/l. Progesterone and RU 38486 (a derivative of 19-nortestosterone with antiglucocorticoid activity) blocked the synergism noted with glucocorticoid and PTH cotreatment, suggesting that interaction between the steroids and PTH was dependent on glucocorticoid receptor interaction. Addition of either 10(-6) mol/l hydrocortisone or 10(-6) mol/l dexamethasone to neonatal mouse calvariae treated with 1,25(OH)(2)-vitamin D-3 (10(-11) and 10(-10) mol/l) also resulted in synergistic stimulation of Ca-45 release. In contrast to these observations, the stimulatory effect of t-RA (10(-8) mol/l) on Ca-45 release from calvarial bones was abolished in the presence of 10(-6) mol/l dexamethasone. These results suggest that an important role of glucocorticoids may be to synergistically potentiate bone resorption stimulated by PTH and 1,25(OH)(2)-vitamin D-3, but indicate an opposing interaction between the glucocorticoids and bone resorptive retinoids.