The effects of chronic prednisone administration on intestinal receptors for 1,25-dihydroxyvitamin D3 in the dog.
Glucocorticoid inhibits intestinal calcium absorption. To further explore the mechanism of this inhibition, we studied dogs during the administration of oral prednisone (1.2-1.5 mg/kg X day) for 20 to 28 weeks in comparison to untreated dogs. Prednisone administration had no effect on serum 25-hydroxyvitamin D concentrations, but was accompanied by a fall in serum 1,25-dihydroxyvitamin D [1,25-(OH)2D] concentrations from 87 +/- 20 pM (control) to 62 +/- 28 pM (prednisone-treated; P less than 0.01). Cytosol prepared from the duodenal, jejunal, and ileal mucosa of control dogs was found to contain a specific 3.2S [3H]1,25-(OH)2D3 binder analogous to the binder that has been observed in the intestine of other species and in other tissues. The apparent concentration of this binder decreased progressively from duodenum to ileum. Prednisone administration increased the apparent duodenal concentration of the binder from 170 +/- 91 (control) to 363 +/- 124 fmol/mg protein (prednisone-treated; P less than 0.025). The intestinal content of calcium-binding protein also declined progressively from the duodenum to the ileum, but was not affected by prednisone administration. These data suggest that events other than alterations in intestinal 1,25-(OH)2D3 receptors must mediate the inhibition of intestinal calcium absorption during chronic glucocorticoid administration.
D000818:Animals; D002112:Calcifediol / Q000097:blood; D002117:Calcitriol / Q000378:metabolism; D002499:Centrifugation, Density Gradient; D003600:Cytosol / Q000032:analysis; D004285:Dogs; D004386:Duodenum / Q000166:cytology; D005260:Female; D007421:Intestine, Small / Q000187:drug effects / Q000378:metabolism*; D007700:Kinetics; D011241:Prednisone / Q000008:administration & dosage / Q000494:pharmacology*; D018167:Receptors, Calcitriol; D011987:Receptors, Steroid / Q000378:metabolism*; D064030:S100 Calcium Binding Protein G / Q000378:metabolism
D018167:Receptors, Calcitriol; D011987:Receptors, Steroid; D064030:S100 Calcium Binding Protein G; D002117:Calcitriol; D002112:Calcifediol; D011241:Prednisone