Differential regulation of PHEX expression in bone and parathyroid gland by chronic renal insufficiency and 1,25-dihydroxyvitamin D3

2004 ◽  
Vol 286 (4) ◽  
pp. F739-F748 ◽  
Author(s):  
Angela J. Brewer ◽  
Lucie Canaff ◽  
Geoffrey N. Hendy ◽  
Harriet S. Tenenhouse
Keyword(s):  
Renal Insufficiency ◽  
Parathyroid Gland ◽  
Chronic Renal Insufficiency ◽  
Control Diet ◽  
Protein Abundance ◽  
Dihydroxyvitamin D3 ◽  
Dihydroxyvitamin D ◽  
Phex Gene ◽  
Rat Tibia ◽  
Serum Pth

Mutations in the PHEX gene are responsible for X-linked hypophosphatemia, a renal phosphate-wasting disorder associated with defective skeletal mineralization. PHEX is predominantly expressed in bones and teeth and in the parathyroid gland of patients with chronic renal failure and tertiary hyperparathyroidism. The purpose of the present study was to examine the effects of renal insufficiency and 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] on the regulation of PHEX expression in rat tibia and parathyroid gland. In rats fed a high-phosphate (Pi) diet, ⅚ nephrectomy elicited a significant increase in the serum parathyroid hormone (PTH) concentration that was associated with a significant increase in the abundance of PHEX mRNA and protein in the tibia and a significant increase in PHEX mRNA in the parathyroid gland. In contrast, 1,25(OH)2D3 administration to intact rats fed a control diet elicited a significant decrease in the serum PTH concentration that was accompanied by a significant decrease in PHEX mRNA and protein abundance in the tibia and a significant decrease in PHEX mRNA in the parathyroid gland. In addition, the increases in serum PTH levels and PHEX mRNA in the tibia and parathyroid gland in ⅚ nephrectomized rats fed a high-Pi diet were blunted by 1,25(OH)2D3. Serum PTH concentration was positively and significantly correlated with tibial PHEX mRNA and protein abundance. In summary, we demonstrate that PHEX expression in the tibia and parathyroid gland is increased by chronic renal insufficiency and decreased by 1,25(OH)2D3 administration and suggest that PTH status may play an important role in mediating these changes in PHEX expression.

Parathyroid gland calcium receptor mRNA levels are unaffected by chronic renal insufficiency or low dietary calcium in rats

Endocrine ◽  
1995 ◽  
Vol 3 (11) ◽  
pp. 769-774 ◽  
Author(s):  
Kimberly V. Rogers ◽  
Rebecca L. Conklin ◽  
Stacey H. Lowe ◽  
Barbara A. Petty
Keyword(s):  
Renal Insufficiency ◽  
Parathyroid Gland ◽  
Chronic Renal Insufficiency ◽  
Dietary Calcium ◽  
Mrna Levels ◽  
Calcium Receptor ◽  
Receptor Mrna

scholarly journals Reduced expression of the renal calcium-sensing receptor in rats with experimental chronic renal insufficiency.

1998 ◽  
Vol 9 (11) ◽  
pp. 2067-2074 ◽  
Author(s):  
R S Mathias ◽  
H T Nguyen ◽  
M Y Zhang ◽  
A A Portale
Keyword(s):  
Renal Insufficiency ◽  
Chronic Renal Insufficiency ◽  
Sham Group ◽  
Ion Homeostasis ◽  
Elevated Serum ◽  
Human Kidney ◽  
Sprague Dawley ◽  
Creatinine Concentration ◽  
Dihydroxyvitamin D ◽  
Protein Levels

Chronic renal insufficiency is associated with elevated serum parathyroid hormone (PTH) levels (2 degrees HPT), deficiency of 1,25-dihydroxyvitamin D (1,25(OH)2D), and hypocalciuria. In chronic renal insufficiency, the 2 degrees HPT may result from reduced expression of the parathyroid gland extracellular Ca(2+)-sensing receptor (CaSR). Since the CaSR was cloned from rat and human kidney, this study examined in rats whether expression of the renal CaSR is altered in experimental chronic renal insufficiency. Four weeks after chronic renal insufficiency was induced by 5/6 nephrectomy (Nx) in Sprague Dawley rats, the serum creatinine concentration was 0.96+/-0.06 mg/dl compared with 0.35+/-0.02 mg/dl in sham-operated animals (P < 0.05). The serum total Ca2+ and phosphorus concentrations were not different. In the Nx group, the serum concentration of amino-PTH was higher (65+/-8 pg/ml), and the concentration of 1,25(OH)2D was significantly lower (47+/-5 pg/ml) compared with 45+/-5 pg/ml and 61+/-4 pg/ml (P = 0.05) in the sham group, respectively. In a subset of rats studied, the Nx group was hypocalciuric (1.4+/-0.5 mg/kg per d) compared with the sham group (3.7+/-0.5 mg/kg per d) (P < 0.05). In the Nx rats, CaSR mRNA expression and CaSR protein levels were found to be reduced by 35 and 38%, respectively, than those observed in controls. These results suggest that reduced renal CaSR expression in chronic renal insufficiency may play a role in disordered mineral ion homeostasis, including hypocalciuria.

Effect of 24R,25-Dihydroxyvitamin D3 in Experimental Renal Insufficiency

1988 ◽  
Vol 16 (4) ◽  
pp. 294-299
Author(s):  
T. Katoh ◽  
Y. Maeda ◽  
H. Yamato ◽  
T. Hirai ◽  
T. Fujii ◽  
...  
Keyword(s):  
Renal Insufficiency ◽  
Immune Function ◽  
Wistar Rats ◽  
Controlled Study ◽  
Dihydroxyvitamin D3 ◽  
Creatinine Excretion ◽  
Urinary Creatinine ◽  
Dihydroxyvitamin D ◽  
Urinary Creatinine Excretion ◽  
Experimentally Induced

This placebo-controlled study in JCL-Wistar rats showed that 100 μg/kg 24 R,25-dihydroxyvitamin D3, when given for 12 days consecutively, restored immune function which had deteriorated following aminonucleoside-induced nephrosis. Urinary creatinine excretion in five-sixths nephrectomized rats was also shown to be increased by 10 μg/kg 24 R,25-dihydroxyvitamin D3. Hypophosphataemic effects in both these cases of experimentally-induced renal insufficiency was also shown following administration of 24 R,25-dihydroxyvitamin D3.

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