Regulation and its refractoriness of 25-hydroxyvitamin D3 metabolism in vitamin D deficiency

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 alpha-hydroxylase activity was reciprocally enhanced concurrently with the decrease in plasma calcium levels. The elevated activity of 1 alpha-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 vitamin D3 to completely suppress renal 1 alpha-hydroxylase activity were 25 micrograms in the 14-day, and 2.5 mg in the 28-day birds. These differences were not observed between the 14-day and 28-day birds when 1 alpha-hydroxyvitamin D3 [1 alpha(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.