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Abnormal skeletal response to parathyroid hormone and the expression of its receptor in chronic uremia

Abstract

Chronic renal failure is characterized by a resistance to the hypercalcemic action of parathyroid hormone (PTH). This resistance probably involves several mechanisms, including a disturbance of vitamin D metabolism, a desensitization of the skeleton by high PTH levels, hyperphosphatemia, uremic toxins, and acidosis. We have explored the possibility that a downregulation of the recently cloned PTH/PTHrp receptor might also be involved. We found a marked decrease in the expression of the receptor mRNA in the kidney and the bone of uremic rats; other authors have found a decrease in the heart and the liver. The reduced expression in the kidney was accompanied by a diminished stimulability of renal adenylate cyclase activity, suggestive of a functional depression of the hormonal response in this target tissue. It is probable that the downregulation of the PTH/PTHrp receptor plays an important role in the skeletal resistance to the calcemic effect of PTH in chronic renal failure.

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Drüeke, T.B. Abnormal skeletal response to parathyroid hormone and the expression of its receptor in chronic uremia. Pediatr Nephrol 10, 348–350 (1996). https://doi.org/10.1007/BF00866780

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key words

  • Hyperparathyroidism
  • Parathyroid hormone
  • Skeletal resistance
  • Parathyroid hormone receptor
  • Renal failure