Acute regulation of parathyroid hormone by dietary phosphate

Secondary hyperparathyroidism in chronic renal failure is stimulated by dietary phosphate (P(i)) loading and ameliorated by dietary P(i) restriction. We investigated the rapidity of the response of serum parathyroid hormone (PTH) to changes in dietary P(i). When uremic rats adapted to a high P(i) diet (HPD) were fed a single meal of low P(i) diet (LPD), plasma PTH fell 80% within 2 h; plasma P(i) fell 1 mg/dl with no change in plasma ionized Ca (ICa). When uremic rats on the HPD were gavaged with LPD, PTH fell 60% within 15 min; plasma P(i) fell by 3.0 mg/dl with no change in total plasma Ca. However, HPD gavage increased PTH by 80% within 15 min with no change in plasma P or Ca, suggesting that the response may be independent of altered plasma P(i). Duodenal infusion of sodium P(i) increased PTH twofold within 10 min, with no change in ICa but an increase in plasma P(i), whereas duodenal infusion of NaCl had no effect on any of these parameters. Intravenous infusion of sodium phosphate also increased PTH within 10 min with no change in plasma ICa; intravenous NaCl had no effect. Additionally, duodenal infusion of phosphonoformate, a nonabsorbable phosphate analog, increased PTH fourfold within 5 min, but did not change plasma P or ICa. These findings indicate that oral P(i) increases PTH release in vivo more rapidly than previously reported; this response may be from both plasma phosphate and an additional signal arising from the gastrointestinal tract.