The renal metabolism of 25-hydroxyvitamin D₃ in the rat: Regulation by 1,25-dihydroxyvitamin D₃

To determine the effects of 1α,25-dihydroxyvitamin D₃ [1,25(OH)₂D₃] on the renal metabolism of 25-hydroxyvitamin D₃ [25(OH)D₃], the influence of 1,25(OH)₂D₃ and 24,25-dihydroxyvitamin D₃ [24,25(OH)₂D₃] was compared in vitamin D-deficient rats. Serum calcium (Ca), serum immunoreactive parathyroid hormone (iPTH) and the specific activities (SA) of renal 25(OH)D₃: 24-hydroxylase (24-hydroxylase) and 25(OH)D₃: 1α-hydroxylase (1-hydroxylase) were measured. In vitamin D-deficient rats, mean serum Ca was low, serum iPTH was increased, renal 1-hydroxylase was increased, and renal 24-hydroxylase was below the limit of detection. Treatment with either 1,25(OH)₂D₃ or 24,25(OH)₂D₃, 50 ng/d for 2 days, significantly increased mean serum Ca but did not change serum iPTH, renal 1-hydroxylase SA, or renal 24-hydroxylase SA. 1,25(OH)₂D₃, 50 ng/d for 7 days, returned serum Ca and iPTH to normal, lowered renal 1-hydroxylase SA, and induced renal 24-hydroxylase activity. In contrast, 24,25(OH)₂D₃, 50 ng/d for 7 days, similarly lowered renal 1-hydroxylase SA but did not induce renal 24-hydroxylase activity. Thyroparathyroidectomy of vitamin D-deficient rats resulted in a rapid decline in 1-hydroxylase SA. The results indicate that in vitamin D-deficient rats a) 1,25(OH)₂D₃ reduces renal 1-hydroxylase SA and increases renal 24-hydroxylase SA and b) 24,25(OH)₂D₃ reduces renal 1-hydroxylase SA and does not alter renal 24-hydroxylase SA. Inhibition of renal 1-hydroxylase by the two metabolites is apparently mediated through changes in serum Ca and circulating iPTH, whereas stimulation by 1,25(OH)₂D₃ of renal 24-hydroxylase activity is direct.