Abstract
Resistance to the action of PTH has been well characterized in the setting of chronic renal failure. Most evidence points to post-receptor abnormalities in its pathogenesis. The recent cloning of the PTH/PTHrP receptor (PTH-R) has permitted us to examine whether in a 5/6 nephrectomy rat model (CRF) the expression of the PTH-R gene is modified. First, we have found that the renal PTH-R mRNA expression is markedly decreased in CRF compared to normal rats. Diminished PTH-R transcripts were associated with a lower PTH-induced cAMP production in renal membranes in CRF suggesting a decrease in the PTH-R number or post-receptor modifications. Second, thyroparathyroidectomized (TPTX) rats with normal renal function had no change in the renal PTH-R expression whereas TPTX-CRF rats still showed a decreased renal PTH-R mRNA expression suggesting that high plasma PTH levels were not etiologically important in the observed down-regulation. Despite the renal PTH-R down-regulation, CRF rats had a normal renal handling of calcium. They also had a higher phosphate excretion than control rats. TPTX-CRF rats showed a decrease in renal tubular calcium reabsorption and a phosphate retention when compared with CRF animals with intact parathyroid glands. This suggests that a few available PTH-R in the kidney allow PTH to exert, to a certain extent, its physiological role in this experimental model of uremia. In conclusion, these findings indicate a down-regulation of the renal PTH-R expression in CRF which appears to be independent of parathyroid gland function. The relevance of this phenomenon in the setting of the secondary hyperparathyroidism of uremia remains to be elucidated.
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Ureña, P., Mannstadt, M., Hruby, M. et al. Down-regulation of the PTH/PTHrP receptor in uremia. J Bone Miner Metab 12 (Suppl 1), S87–S90 (1994). https://doi.org/10.1007/BF02375682
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DOI: https://doi.org/10.1007/BF02375682