Abnormal skeletal response to parathyroid hormone and the expression of its receptor in chronic uremia.
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 PTII in chronic renal failure.
Drüeke
T B
TB
INSERM Unité 90, Hôpital Necker, Paris, France.
D000818:Animals; D001842:Bone and Bones / Q000503:physiopathology*; D002648:Child; D006801:Humans; D007676:Kidney Failure, Chronic / Q000378:metabolism* / Q000503:physiopathology*; D010281:Parathyroid Hormone / Q000502:physiology*; D051381:Rats; D018016:Receptors, Parathyroid Hormone / Q000096:biosynthesis*
D010281:Parathyroid Hormone; D018016:Receptors, Parathyroid Hormone