title: Parathyroid hyperplasia in uremic rats precedes down-regulation of the calcium receptor.
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.
  
  
  CONCLUSIONS
  These data indicate that parathyroid cell hyperplasia precedes down-regulation of CaR expression in the uremic rat model.
authors.affiliation: Renal Division, Washington University Medical School, St. Louis, Missouri 63110, USA.
authors.forename: C S
authors.initials: CS
authors.lastname: Ritter
authors.forename: J L
authors.initials: JL
authors.lastname: Finch
authors.forename: E A
authors.initials: EA
authors.lastname: Slatopolsky
authors.forename: A J
authors.initials: AJ
authors.lastname: Brown
mesh_terms: D000818:Animals; D015536:Down-Regulation; D005260:Female; D006965:Hyperplasia; D010280:Parathyroid Glands / Q000473:pathology*; D010710:Phosphates / Q000008:administration & dosage; D018809:Proliferating Cell Nuclear Antigen / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D044169:Receptors, Calcium-Sensing; D011956:Receptors, Cell Surface / Q000032:analysis*; D014511:Uremia / Q000473:pathology*
chemical_list: D010710:Phosphates; D018809:Proliferating Cell Nuclear Antigen; D044169:Receptors, Calcium-Sensing; D011956:Receptors, Cell Surface; C473605:extracellular calcium cation-sensing receptor, rat