Calcitonin stimulation of renal 25-hydroxyvitamin D-1 alpha-hydroxylase activity in hypophosphatemic mice. Evidence that the regulation of calcitriol production is not universally abnormal in X-linked hypophosphatemia.
Hypophosphatemia (Hyp) mice have defective regulation of 25(OH)D-1 alpha-hydroxylase activity in response to hypophosphatemia, hypocalcemia, and parathyroid hormone (PTH) administration. However, recent observations support the existence of anatomically distinct, independently regulated renal 1 alpha-hydroxylase systems in mammalian proximal convoluted and straight tubules. To more completely define the extent of the 1 alpha-hydroxylase regulatory defect in Hyp-mice, we compared enzyme maximum velocity in normal and mutants after infusion of calcitonin. Upon stimulation, renal 1 alpha-hydroxylase activity increased to similar levels in normal and Hyp-mouse renal homogenates. Moreover, time-course and dose-dependence studies revealed similar patterns of response in the animal models. Subsequently, we examined whether PTH and calcitonin stimulatory effects on enzyme activity are mediated through different mechanisms. In both animal models administration of PTH and calcitonin increased enzyme activity to levels greater than those obtained after maximal stimulation by either hormone alone, consistent with additive effects. These observations indicate that a calcitonin-sensitive component of 1 alpha-hydroxylase is not compromised in the X-linked hypophosphatemic syndrome.
D015090:25-Hydroxyvitamin D3 1-alpha-Hydroxylase / Q000378:metabolism*; D000818:Animals; D002116:Calcitonin / Q000494:pharmacology*; D002117:Calcitriol / Q000096:biosynthesis*; D004789:Enzyme Activation; D007015:Hypophosphatemia, Familial / Q000378:metabolism*; D007668:Kidney / Q000201:enzymology; D051379:Mice; D010281:Parathyroid Hormone / Q000494:pharmacology; D013250:Steroid Hydroxylases / Q000378:metabolism*; D014960:X Chromosome
D010281:Parathyroid Hormone; D002116:Calcitonin; D013250:Steroid Hydroxylases; D015090:25-Hydroxyvitamin D3 1-alpha-Hydroxylase; D002117:Calcitriol