Inhibitory and stimulatory effects of dexamethasone and 1,25-dihydroxyvitamin D 3 on chick intestinal calbindin-D 28K and its mRNA

Abstract

The present study examined the interactions of the synthetic glucocorticoid, dexamethasone, with the regulation of chick intestinal calbindin-D 28K (a 28 000 Da vitamin D-dependent calcium binding protein, CaBP) and its mRNA by 1,25-dihydroxyvitamin D 3 (1,25(OH) 2D 3). Dexamethasone (0–500 nmol) had a neutral impact on calbindin levels in the rachitic chick intestine when measured 12 h later. However, dexamethasone appeared to exert a significant, though modest, stimulatory influence upon calbindin-mRNA accumulation in the vitamin D-deficient (−D) intestine when measured 12 h after administration. 1,25(OH) 2D 3 also stimulated calbindin-mRNA accumulation in the −D chick intestine; half-maximal (ED 50) doses were 1.1 nmol (7.6-fold) and 12.6 nmol (4.3-fold stimulation) for 1,25(OH) 2D 3 and dexamethasone respectively. In contrast, when both 1,25(OH) 2D 3 and dexamethasone were administered simultaneously, the stimulatory effect of 1,25(OH) 2D 3 (and that of the glucocorticoid) was lost in terms of calbindin and calbindin-mRNA accumulation. Dexamethasone treatment of vitamin D-replete (+D) chicks resulted in a depression of calbindin-mRNA accumulation; levels were depressed to baseline with 250 nmol/bird. Dexamethasone (1.25 μmol per day for 3 days) also induced an apparent ‘down-regulation’ of the 1,25(OH) 2D 3 receptor population in the −D chick intestine but failed to influence the binding of 1,25(OH) 2D 3 to its receptor in vitro. Taken collectively, these data indicate that glucocorticoids are able to influence the receptor-mediated action of 1,25(OH) 2D 3, possibly at the level of calbindin-D 28K gene expression.