PARATHYROID CELL-PROLIFERATION IN NORMAL AND CHRONIC-RENAL-FAILURE RATS - THE EFFECTS OF CALCIUM, PHOSPHATE, AND VITAMIN-D

Secondary hyperparathyroidism is characterized by an increase in parat hyroid (PT) cell number, and parathyroid hormone (PTH) synthesis and s ecretion, It is still unknown as to what stimuli regulate PT cell prol iferation and how they do this, We have studied rats with dietary-indu ced secondary hyper- and hypoparathyroidism, rats given 1,25-dihgdroxy vitamin D-3 (1,25(OH)(2)D-3) and rats after 5/6 nephrectomy for the pr esence of PT cell proliferation and apoptosis. PT cell proliferation h as been measured by staining for proliferating cell nuclear antigen (P CNA) and apoptosis by in situ detection of nuclear DNA fragmentation a nd correlated with serum biochemistry and PTH mRNA levels, A low calci um diet led to increased levels of PTH mRNA and a 10-fold increase in PT cell proliferation, A low phosphate diet led to decreased levels of PTH mRNA and the complete absence of PT cell proliferation. 1,25(OH)( 2)D-3 (25 pmol/d x 3) led to a decrease in PTH mRNA levels and unlike the hypophosphatemic rats there was no decrease in cell proliferation. There were no cells undergoing apoptosis in any of the experimental c onditions, The secondary hyperparathyroidism of 5/6 nephrectomized rat s was characterized by an increase in PTH mRNA levels and PT cell prol iferation which were both markedly decreased by a low phosphate diet. The number of PCNA positive cells was increased by a high phosphate di et, Therefore hypocalcemia, hyperphosphatemia and uremia lead to PT ce ll proliferation, and hypophosphatemia completely abolishes this effec t, Injected 1,25(OH)(2)D-3 had no effect. These findings emphasize the importance of a normal phosphate and calcium in the prevention of PT cell hyperplasia.