Rat calcium-sensing receptor is regulated by vitamin D but not by calcium

Parathyroid hormone (PTH) secretion is regulated by extracellular calcium acting through a cell surface calcium receptor (CaR). We have examined the potential regulation of the CaR in the parathyroid glands (PTG) and kidney by calcium and 1,25-dihydroxyvitamin D-3 [1,25-(OH)(2)D-3]. Rats fed vitamin D-deficient (-D) diets containing 0.02, 0.4, or 2.0% Ca had a wide range of serum ionized Ca (2.5-5.2 mg/dl) and PTH (22-590 pg/ml) concentrations. PTG CaR mRNA did not vary significantly with ionized calcium or PTH, indicating that hypocalcemia and hyperparathyroidism may not alter CaR expression. However, PTG CaR mRNA was 40% lower in the -D rats than in age-matched rats fed a vitamin D-replete (+D) diet (P < 0.002). Repletion of -D rats with 1,25-(OH)(2)D-3 produced a dose-dependent increase in PTG CaR mRNA. Treatment of +D rats with 100 ng of 1,25-(OH)(2)D-3 increased CaR mRNA by 33% (P < 0.05) and 54% (P < 0.002) in the PTG and by 89% (P < 0.02) and 91% (P < 0.02) in the kidney in two independent experiments. PTG CaR peaked at 16 h (150% of control, P < 0.05) after 1,25-(OH)(2)D-3 administration but returned to normal by 24 h. This upregulation of CaR expression by 1,25-(OH)(2)D-3 may be involved in the suppressive effects of vitamin D compounds on PTH secretion.