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

Background. Recent evidence points to a relationship between the down-regul ation of the calcium-sensing receptor (CaR) and parathyroid cell hyperplasi a 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 su bsequently 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 h yperplasia, or (2) maintained on a low phosphate (LP) diet that inhibits de velopment 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 b y immunohistochemistry. Results. When rats were nephrectomized and placed immediately on a HP diet, parathyroid cell proliferation was significantly increased by day 2 and co ntinued to increase at day 4. CaR content was unchanged at 1 and 2 days pos t-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 parathy roid cell proliferation was again seen at day 2; downregulation 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 uremia rat model.