HIGH PHOSPHATE LEVEL DIRECTLY STIMULATES PARATHYROID-HORMONE SECRETION AND SYNTHESIS BY HUMAN PARATHYROID TISSUE IN-VITRO

Phosphate retention plays an important role in the pathogenesis of sec ondary hyperparathyroidism in patients with renal failure. In in vitro studies, high extracellular phosphate levels directly stimulate PTH s ecretion in rat and bovine parathyroid tissue. The present study evalu ates the effect of high phosphate levels on the secretion of PTH and t he production of prepro PTH mRNA in human hyperplastic parathyroid gla nds. The study includes parathyroid glands obtained from patients with primary adenomas and from hemodialysis and kidney-transplant patients with diffuse and nodular secondary hyperplasia. The experiments were performed in vitro using small pieces of parathyroid tissue. The abili ty of high calcium levels to decrease PTH secretion was less in adenom as than in secondary hyperplasia; among the secondary hyperplasia, nod ular was less responsive to an increase in calcium than diffuse hyperp lasia. In diffuse hyperplasia, PTH secretion was increased in response to 3 and 4 mM phosphate compared with 2 mM phosphate, despite a high calcium concentration in the medium; prepro PTH mRNA levels increased after incubation in 4 mM phosphate. Similar results were obtained with nodular hyperplasia, except that the elevation of PTH secretion in re sponse to 3 mM phosphate did not attain statistical significance. In a denomas, high calcium concentrations (1.5 mM) did not result in inhibi tion of PTH secretion, independent of the phosphate concentration, and the prepro PTH mRNA was not significantly increased by high phosphate levels. In conclusion, first, the PTH secretory response to an increa se in calcium concentration is less in nodular than diffuse hyperplasi a; second, high phosphate levels directly affect PTH secretion and gen e expression in patients with advanced secondary hyperparathyroidism.