Metabolic consequences of oral administration of 24,25-dihydroxycholecalciferol to uremic dogs.
24,25-dihydroxycholecalciferol [24,25-(OH)(2)D(3)], once considered a relatively inert metabolite of vitamin D(3), has been recently recognized as a metabolically active product in some species. In previous studies, we have shown that infusion of 24,25(OH)(2)D(3) into the thyroid artery of normal dogs results in prompt and complete suppression of parathyroid hormone (PTH) secretion. In this study, we have examined the metabolic consequences of oral administration of this metabolite in dogs with experimentally induced renal hyperparathyroidism. Dogs with comparable degrees of renal insufficiency (glomerular filtration rate, 10-15 ml/min) were treated for 3 wk with daily doses of either 2 mug of 24,25(OH)(2)D(3) or 50% ethanol, the vehicle in which the metabolite was suspended. After a 6-wk recovery period, treatments were reversed: dogs who had previously served as controls received the metabolite while dogs previously treated with metabolite received the vehicle. Administration of 24,25(OH)(2)D(3) resulted in a 40-60% decrease of immunoreactive PTH. This was associated with a small (0.1-0.2 mg/dl) but unequivocal decrease of serum ionized calcium. Calcium balance, which was slightly negative under control conditions, became slightly but definitively positive on treatment with 24,25(OH)(2)D(3). All other parameters measured, including total serum calcium, magnesium, phosphorus, creatinine, electrolytes, phosphorus excretion, and phosphorus balance, remained unchanged. The data support the hypothesis that 24,25(OH)(2)D(3) not only decreases PTH secretion but also functions as an anabolic hormone in bone under the conditions of this experiment.
D000284:Administration, Oral; D000818:Animals; D002118:Calcium / Q000097:blood / Q000378:metabolism; D012080:Chronic Kidney Disease-Mineral and Bone Disorder / Q000188:drug therapy / Q000378:metabolism*; D004100:Dihydroxycholecalciferols / Q000008:administration & dosage / Q000378:metabolism* / Q000627:therapeutic use; D004285:Dogs; D005260:Female; D006887:Hydroxycholecalciferols / Q000378:metabolism*; D010281:Parathyroid Hormone / Q000097:blood
D004100:Dihydroxycholecalciferols; D006887:Hydroxycholecalciferols; D010281:Parathyroid Hormone; D002118:Calcium