Parathyroid hyperplasia in uremic rats precedes down-regulation of the calcium receptor

Kidney Int. 2001 Nov;60(5):1737-44. doi: 10.1046/j.1523-1755.2001.00027.x.

Abstract

Background: Recent evidence points to a relationship between the down-regulation of the calcium-sensing receptor (CaR) and parathyroid cell hyperplasia that is associated with chronic renal failure. It is not known, however, if down-regulation of the CaR precedes, and perhaps initiates, parathyroid cell proliferation, or if a decrease in the expression of the CaR occurs subsequently to hyperplasia or the conditions promoting it. The current study examined the temporal relationship of these two events.

Methods: Rats were made uremic by subtotal nephrectomy and were (1) placed immediately on a high phosphate (HP) diet that promotes parathyroid gland hyperplasia, or (2) maintained on a low phosphate (LP) diet that inhibits development of secondary hyperparathyroidism before being switched to the HP diet. Serum chemistries and parathyroid gland (PTG) weights were examined; CaR content and parathyroid cell proliferation (PCNA/Ki-67) were analyzed by immunohistochemistry.

Results: When rats were nephrectomized and placed immediately on a HP diet, parathyroid cell proliferation was significantly increased by day 2 and continued to increase at day 4. CaR content was unchanged at 1 and 2 days post-nephrectomy, but fell by day 4. When nephrectomized rats were maintained for 1 week on a LP diet, then switched to a HP diet, an increase in parathyroid cell proliferation was again seen at day 2; down-regulation of the CaR did not occur until after 7 days of uremia and the HP diet.

Conclusion: These data indicate that parathyroid cell hyperplasia precedes down-regulation of CaR expression in the uremic rat model.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Down-Regulation
  • Female
  • Hyperplasia
  • Parathyroid Glands / pathology*
  • Phosphates / administration & dosage
  • Proliferating Cell Nuclear Antigen / analysis
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, Calcium-Sensing
  • Receptors, Cell Surface / analysis*
  • Uremia / pathology*

Substances

  • Phosphates
  • Proliferating Cell Nuclear Antigen
  • Receptors, Calcium-Sensing
  • Receptors, Cell Surface
  • extracellular calcium cation-sensing receptor, rat