title: Reversal of skeletal resistance to parathyroid hormone in uremia by vitamin D metabolites: evidence for the requirement of 1,25(OH)2D3 and 24,25(OH)2D3.
abstract: This study evaluates the role of vitamin D metabolites in the genesis of the skeletal resistance to the calcemic action of PTH in uremia. The changes in serum calcium after infusion of 2 U of PTE per kilogram per hour for 8 hr were evaluated in thyroparathyroidectomized dogs before and after 1 and 3 days of acute uremia produced by bilateral nephrectomy. The animals received vitamin D metabolites during the 3 days of uremia. Supplementation of 0.68 microgram/day 1,25(OH)2D3 and 24R,25(OH)2D3 restored the calcemic response to PTE to normal. This is in contrast to only partial correction of the response to PTE by 1,25(OH)2D3 alone. Administration of 1.36 microgram/day 24R,25(OH)2D3 did not improve the calcemic response to PTE. The results indicate that (1) both 1,25(OH)2D3 and 24R,25(OH)2D3 are necessary for the complete reversal of the impaired calcemic response to PTE, (2) this effect is not due to the increase in the amount of the dihydroxylated compounds of vitamin D, since equivalent amounts of these compounds in the form of 24R,25(OH)2D3 alone had no effect, and (3) the better effect of the combination of 1,25(OH)2D3 and 24R,25(OH)2D3 is most probably due to an interaction between these two metabolites of vitamin D permitting an intact calcemic action of PTH.
mesh_terms: D000818:Animals; D002118:Calcium / Q000097:blood*; D003404:Creatinine / Q000097:blood; D004100:Dihydroxycholecalciferols / Q000627:therapeutic use*; D004285:Dogs; D004351:Drug Resistance; D005260:Female; D006887:Hydroxycholecalciferols / Q000627:therapeutic use*; D008297:Male; D009392:Nephrectomy; D010281:Parathyroid Hormone / Q000627:therapeutic use*; D010758:Phosphorus / Q000097:blood; D014511:Uremia / Q000503:physiopathology*
chemical_list: D004100:Dihydroxycholecalciferols; D006887:Hydroxycholecalciferols; D010281:Parathyroid Hormone; D010758:Phosphorus; D003404:Creatinine; D002118:Calcium