Parathyroidectomy does not prevent the renal PTH/PTHrP receptor down-regulation in uremic rats.
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)
Ureña
P
P
INSERM Unité 90, Hôpital Necker, Paris, France.
Mannstadt
M
M
Hruby
M
M
Ferreira
A
A
Schmitt
F
F
Silve
C
C
Ardaillou
R
R
Lacour
B
B
Abou-Samra
A B
AB
Segre
G V
GV
D000262:Adenylyl Cyclases / Q000378:metabolism; D000818:Animals; D001483:Base Sequence; D001769:Blood / Q000378:metabolism; D015536:Down-Regulation; D007668:Kidney / Q000378:metabolism*; D008297:Male; D015335:Molecular Probes / Q000235:genetics; D008969:Molecular Sequence Data; D009693:Nucleic Acid Hybridization; D016105:Parathyroidectomy; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D044168:Receptor, Parathyroid Hormone, Type 1; D018016:Receptors, Parathyroid Hormone / Q000235:genetics / Q000378:metabolism*; D013965:Thyroidectomy; D014511:Uremia / Q000378:metabolism*; D014556:Urine / Q000737:chemistry
D015335:Molecular Probes; D012333:RNA, Messenger; D044168:Receptor, Parathyroid Hormone, Type 1; D018016:Receptors, Parathyroid Hormone; D000262:Adenylyl Cyclases