Effect of parathyroid hormone on cAMP and 1,25-dihydroxyvitamin D formation and renal handling of phosphate in vitamin D-dependent rickets.
Studies were carried out to compare the effects of parathyroid extract (PTE) on the serum concentration of 1,25-dihydroxyvitamin D (1,25[OH]2D), 24,25-dihydroxyvitamin D (24,25[OH]2D), 25,26-dihydroxy vitamin D (25,26[OH]2D) and cAMP, and the urinary excretion of calcium, phosphorus, and cAMP in two normal adult subjects, and in a girl with vitamin D-dependent rickets. The concentration of 1,25[OH]2D was markedly decreased even when she was receiving a daily dose of 25,000 IU of ergocalciferol. PTE infusion resulted in a prompt and distinct increase in the serum levels and the urinary excretion of cAMP in the patient and control subjects. In the control subjects the serum concentration of 1,25[OH]2D increased after the PTE infusion, whereas there was no response in the patient with vitamin D-dependent rickets. The two other dihydroxylated metabolites of vitamin D showed no consistent response to the PTE infusion in the control subjects or the patient. The patient showed no phosphaturic response to PTE while she was receiving high-dosage ergocalciferol treatment. By contrast, when the patient was re-studied after therapy with 1 alpha-hydroxyvitamin D, PTE infusion resulted in an increase in urinary phosphate excretion. These findings might lend support for the notion that 1,25[OH]2D has an effect on tubular phosphate resorption and has a permissive role in the phosphaturic effect of parathyroid hormone. The present findings also confirm that the formation of 1,25[OH]2D is impaired in vitamin D-dependent rickets and indicate that the renal 25-hydroxyvitamin D-1 alpha-hydroxylase is unresponsive to the stimulatory effect of parathyroid hormone in this condition.
D015090:25-Hydroxyvitamin D3 1-alpha-Hydroxylase; D000242:Cyclic AMP / Q000096:biosynthesis*; D004100:Dihydroxycholecalciferols / Q000096:biosynthesis*; D005260:Female; D006801:Humans; D007015:Hypophosphatemia, Familial / Q000188:drug therapy* / Q000378:metabolism; D007223:Infant; D007668:Kidney / Q000378:metabolism*; D010281:Parathyroid Hormone / Q000627:therapeutic use*; D010710:Phosphates / Q000378:metabolism*; D013250:Steroid Hydroxylases / Q000378:metabolism
D004100:Dihydroxycholecalciferols; D010281:Parathyroid Hormone; D010710:Phosphates; D000242:Cyclic AMP; D013250:Steroid Hydroxylases; D015090:25-Hydroxyvitamin D3 1-alpha-Hydroxylase