Regulation and Its Refractoriness of 25-Hydroxyvitamin D₃ Metabolism in Vitamin D Deficiency

Abstract

The time course of change in plasma calcium levels and renal metabolism of 25-hydroxyvitamin D₃ [25(OH)D₃] was investigated in chicks maintained on a vitamin D-deficient diet for 4 weeks. Plasma calcium concentrations dropped sharply between the 7th and 14th day of the feeding period. Renal 25(OH)D₃-1 α-hydroxylase activity was reciprocally enhanced concurrently with the decrease in plasma calcium levels. The elevated activity of 1 α-hydroxylase had declined significantly by the 21st and 28th days in spite of the more severe hypocalcemia. When graded amounts of vitamin D₃ were administered to the chicks maintained on this diet for 14 or 28 days, there were considerable differences in the change of plasma calcium levels and 25(OH)D₃ metabolism induced by vitamin D₃ administration between the 14-day and 28-day birds. The minimal dose levels of vitaminD3 to completely suppress renal 1 α-hydroxylase activity were 25μg in the 14-day, and 2.5mg in the 28-day birds. These differences were not observed between the 14-day and 28-day birds when l xhydroxyvitamin D₃ [lα(OH)D₃] was administered. Renal adenylate cyclase activity induced by parathyroid hormone (PTH) was much lower in the 28-day chicks than that in 1-day-old and the 14-day birds. These results are explained by the hypersecretion of PTH and the subsequent refractoriness of the target organs in severe vitamin D deficiency. Plasma calcium levels per se did not appear to be a major factor in the regulation of 25(OH)D₃ metabolism.