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Parathyroidectomy does not prevent the renal PTH/PTHrP receptor down-regulation in uremic rats
P Ureña1, M Mannstadt, M Hruby
1INSERM Unité 90, Hôpital Necker, Paris, France.
Abstract:
In a recent study we demonstrated that the PTH/PTHrP receptor (PTH-R) mRNA was markedly down-regulated in the remnant kidney of uremic rats with severe secondary hyperparathyroidism. Among the factors potentially implicated in this down-regulation, to date only PTH has been demonstrated to modulate PTH-R expression. Here, we examined the effect of thyroparathyroidectomy (TPTX) on the renal expression of PTH-R in rats with normal renal function or with chronic renal failure (CRF) induced by 5/6 nephrectomy. Four groups of rats were studied: control, TPTX, CRF, and CRF + TPTX. Moderate-degree renal failure was documented by mean (+/- SD) creatinine clearances (microliter/min/100 g body wt) of 259 +/- 40 and 212 +/- 45 in CRF and CRF + TPTX rats, compared with 646 +/- 123 and 511 +/- 156 in control and TPTX rats, respectively. Plasma phosphorus, calcitriol, and ionized calcium were significantly lower in CRF and CRF + TPTX than in control animals. Plasma ionized calcium and calcitriol were also lower in TPTX than in control rats. Plasma PTH levels (pg/ml) were increased in CRF rats (41.8 +/- 29.4), and markedly decreased in TPTX (10.1 +/- 7.8) and CRF + TPTX (8.0 +/- 3.8) rats compared with control rats (21.7 +/- 7.5). Northern blot analysis showed that the level of the steady-state PTH-R mRNA in the kidney of CRF and CRF + TPTX rats was markedly decreased compared with that of control rats, the ratios of PTH-R mRNA/beta-actin mRNA being 0.28 +/- 0.04 and 0.27 +/- 0.03 versus 0.54 +/- 0.05, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)
Insights
Thyroparathyroidectomy (TPTX) down-regulates the PTH/PTHrP receptor (PTH-R) mRNA in rat kidneys, even in chronic renal failure (CRF). This suggests PTH-R expression is sensitive to parathyroid hormone levels.
Area of Science:
- Nephrology
- Endocrinology
- Molecular Biology
Background:
- Secondary hyperparathyroidism in chronic renal failure (CRF) is associated with down-regulated PTH/PTHrP receptor (PTH-R) mRNA in remnant kidneys.
- Parathyroid hormone (PTH) is known to modulate PTH-R expression.
Purpose of the Study:
- To investigate the effect of thyroparathyroidectomy (TPTX) on renal PTH-R mRNA expression in rats with normal renal function and CRF.
- To understand the role of parathyroid glands in regulating renal PTH-R expression.
Main Methods:
- Four groups of rats were studied: control, TPTX, CRF, and CRF + TPTX.
- Chronic renal failure (CRF) was induced by 5/6 nephrectomy.
- Renal PTH-R mRNA levels were analyzed using Northern blot analysis.
Main Results:
- TPTX significantly decreased plasma PTH levels in both normal and CRF rats.
- Renal PTH-R mRNA was markedly decreased in CRF rats compared to control rats.
- TPTX did not further decrease the already low PTH-R mRNA levels in CRF rats, indicating PTH-R expression is sensitive to PTH levels.
Conclusions:
- Renal PTH-R mRNA expression is significantly reduced in chronic renal failure.
- Thyroparathyroidectomy leads to down-regulation of renal PTH-R mRNA, suggesting a role for parathyroid hormone in its regulation.
- These findings highlight the complex interplay between PTH, renal function, and PTH-R expression.