GLUCOCORTICOID REGULATION OF CALCITONIN RECEPTOR IN MOUSE OSTEOCLAST-LIKE MULTINUCLEATED CELLS

Abundant multinucleated cells (MNCs) are formed in cocultures of mouse osteoblastic cells and marrow cells in the presence of 1 alpha, 25-di hydroxyvitamin D-3 [1 alpha, 25(OH)(2)D-3], and these cells have the p roperties of osteoclasts (OCs). In this study using the mammalian OCs, we tried to clarify the role of glucocorticoids (GCs) in calcitonin r eceptors (CTR) and CT-responsive cAMP production in OCs. Dexamethasone (DEX) dose and time dependently enhanced the specific binding of [I-1 25]salmon calcitonin (sCT). When the MNCs were preincubated with DEX f or 24 h, the effect was evident at 10(-9) M and the maximum effect was obtained at 10(-7) M. The effect developed over 12-48 h at doses of 1 0(-9) and 10(-6) M DEX. The numbers of CTR-positive mononuclear cells and MNCs were not altered by the DEX treatment. Prednisolone and triam cinolone reproduced the DEX effect, but 17 beta-estradiol, progesteron e, testosterone, aldosterone, and 1 alpha, 25(OH)(2)D-3 did not. RU486 , a GC receptor antagonist, attenuated the effect of DEX to enhance th e specific binding of [I-125]sCT. From a Scatchard plot analysis, DEX enhanced CTR number (212 +/- 64%) with a minimal change in the affinit y to sCT. Autoradiographic studies using [I-125]sCT showed that DEX en hanced the density of the grains on the tartrate-resistant acid phosph atase (TRAP)-positive MNCs and mononuclear cells, but not on other typ es of cells. DEX preincubation also enhanced sCT-stimulated but not pr ostaglandin E(2)- or forskolin-stimulated cAMP production. Inhibition of enhancement was possible with cycloheximide, indicating this effect was mediated through de novo protein synthesis. The present study sho wed that GCs play an important role in the regulation of CT effect thr ough the upregulation of CTR on OCs, and this effect would explain, at least partly, a potentiation by GCs of hypocalcemic action of CT in h ypercalcemic patients.