title: Differential effects of glucocorticoids on bone resorption in neonatal mouse calvariae stimulated by peptide and steroid-like hormones.
abstract: 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 D3, all trans-retinoic acid (t-RA), or prostaglandin E2 (PGE2). Bone resorption was assessed by analyzing either the release of 45Ca from [45Ca]CaCl2 prelabeled calvarial bones or the release of 3H from [3H]proline prelabeled calvariae. At PGE2 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 45Ca release from neonatal mouse calvariae. In contrast, synergistic release from mouse calvarial bones of both 45Ca and 3H 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 45Ca 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 co-treatment, 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 D3 (10(-11) and 10(-10) mol/l) also resulted in synergistic stimulation of 45Ca release. In contrast to these observations, the stimulatory effect of t-RA (10(-8) mol/l) on 45Ca 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 D3, but indicate an opposing interaction between the glucocorticoids and bone resorptive retinoids.
authors.affiliation: Department of Physiology and Biophysics, University of Arkansas for Medical Sciences, Little Rock 72205, USA.
authors.forename: H H
authors.initials: HH
authors.lastname: Conaway
authors.forename: D
authors.initials: D
authors.lastname: Grigorie
authors.forename: U H
authors.initials: UH
authors.lastname: Lerner
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001862:Bone Resorption; D002117:Calcitriol / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism; D046508:Culture Techniques; D003907:Dexamethasone / Q000494:pharmacology; D015232:Dinoprostone / Q000494:pharmacology*; D004357:Drug Synergism; D005938:Glucocorticoids / Q000494:pharmacology*; D006854:Hydrocortisone / Q000494:pharmacology; D051379:Mice; D008815:Mice, Inbred Strains; D010281:Parathyroid Hormone / Q000494:pharmacology*; D011392:Proline / Q000378:metabolism; D012886:Skull; D013268:Stimulation, Chemical; D014212:Tretinoin / Q000494:pharmacology*; D014316:Tritium / Q000378:metabolism
chemical_list: D005938:Glucocorticoids; D010281:Parathyroid Hormone; D014316:Tritium; D014212:Tretinoin; D003907:Dexamethasone; D011392:Proline; D002117:Calcitriol; D015232:Dinoprostone; D002118:Calcium; D006854:Hydrocortisone