Inhibitory and stimulatory effects of dexamethasone and 1,25-dihydroxyvitamin D3 on chick intestinal calbindin-D28K and its mRNA.
The present study examined the interactions of the synthetic glucocorticoid, dexamethasone, with the regulation of chick intestinal calbindin-D28K (a 28,000 Da vitamin D-dependent calcium binding protein, CaBP) and its mRNA by 1,25-dihydroxyvitamin D3 (1,25(OH)2D3). 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)2D3 also stimulated calbindin-mRNA accumulation in the -D chick intestine; half-maximal (ED50) doses were 1.1 nmol (7.6-fold) and 12.6 nmol (4.3-fold stimulation) for 1,25(OH)2D3 and dexamethasone respectively. In contrast, when both 1,25(OH)2D3 and dexamethasone were administered simultaneously, the stimulatory effect of 1,25(OH)2D3 (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 mumol per day for 3 days) also induced an apparent 'down-regulation' of the 1,25(OH)2D3 receptor population in the -D chick intestine but failed to influence the binding of 1,25(OH)2D3 to its receptor in vitro. Taken collectively, these data indicate that glucocorticoids are able to influence the receptor-mediated action of 1,25(OH)2D3, possibly at the level of calbindin-D28K gene expression.
D000818:Animals; D064026:Calbindins; D002117:Calcitriol / Q000494:pharmacology* / Q000502:physiology; D002135:Calcium-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D002645:Chickens; D003907:Dexamethasone / Q000494:pharmacology*; D004386:Duodenum / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000187:drug effects; D007413:Intestinal Mucosa / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics; D018167:Receptors, Calcitriol; D011987:Receptors, Steroid / Q000378:metabolism; D064030:S100 Calcium Binding Protein G / Q000378:metabolism*; D014808:Vitamin D Deficiency / Q000503:physiopathology
D064026:Calbindins; D002135:Calcium-Binding Proteins; D012333:RNA, Messenger; D018167:Receptors, Calcitriol; D011987:Receptors, Steroid; D064030:S100 Calcium Binding Protein G; D003907:Dexamethasone; D002117:Calcitriol