Hormones – Cytokines – Signaling
Kidney International (1999) 55, 1284–1292; doi:10.1046/j.1523-1755.1999.00386.x
Decreased calcium-sensing receptor expression in hyperplastic parathyroid glands of uremic rats: Role of dietary phosphate
Alex J Brown, Cynthia S Ritter, Jane L Finch and Eduardo A Slatopolsky
Renal Division, Washington University Medical School, St. Louis, Missouri, USA
Correspondence: Dr Alex J. Brown, Box 8126, Washington University Medical School, St. Louis, Missouri 63110, USA. E-mail: abrown@imgate.wustl.edu
Received 13 February 1998; Revised 15 October 1998; Accepted 17 November 1998.
Abstract
Decreased calcium-sensing receptor expression in hyperplastic parathyroid glands of uremic rats: Role of dietary phosphate.
Background
The abnormal control of parathyroid hormone secretion in chronic renal failure is attributed, in part, to down-regulation of the calcium-sensing receptor (CaR) in hyperplastic parathyroid tissue. The cause of this down-regulation is unknown. Here we examined the roles of uremia and parathyroid hyperplasia on parathyroid gland (PTG) CaR expression in the rat model of renal failure.
Methods
Rats made uremic by 5/6 nephrectomy were maintained for one month on diets containing 0.2% P (low phosphate), 0.5% P (normal phosphate) or 1.2% P (high phosphate); intact rats (controls) were maintained on the normal-phosphate diet.
Results
CaR mRNA was reduced only in uremic rats fed the high-phosphate diet (55% less than in controls, P < 0.05). Immunohistochemical staining revealed decreased CaR protein expression in uremic high-phosphate rat PTG compared with controls (41% decrease as determined by computer-assisted quantitation, P < 0.01). PTG size was increased in uremic rats fed the high-phosphate diet compared with controls (2.77 
0.95 vs. 0.77 0.16 
g/g body wt, P < 0.0001). There was no increase in PTG size in uremic rats fed the low-phosphate and normal-phosphate diets (0.92 0.31 and 1.01 0.31 g/g) compared with controls (0.77 0.16 g/g body wt). Immunohistochemical staining for proliferating cell nuclear antigen in hyperplastic PTG from uremic rats showed that CaR was decreased primarily in areas of active cell proliferation.
Conclusion
These results suggest that CaR down-regulation cannot be attributed to uremia per se, but rather, is associated with parathyroid cell proliferation. Furthermore, dietary phosphate restriction prevents both the parathyroid hyperplasia and decreased CaR expression in renal failure.
Keywords:
receptor, parathyroid hyperplasia, uremia, chronic renal failure, diet, calcium homeostasis
