Phosphorus restriction prevents parathyroid gland growth. High phosphorus directly stimulates PTH secretion in vitro

J Clin Invest. 1996 Jun 1;97(11):2534-40. doi: 10.1172/JCI118701.


Dietary phosphorus (P) restriction is known to ameliorate secondary hyperparathyroidism in renal failure patients. In early renal failure, this effect may be mediated by an increase in 1,25-(OH)2D3, whereas in advanced renal failure, P restriction can act independent of changes in 1,25-(OH)2D3 and serum ionized calcium (ICa). In this study, we examined the effects of dietary P on serum PTH, PTH mRNA, and parathyroid gland (PTG) hyperplasia in uremic rats. Normal and uremic rats were maintained on a low (0.2%) or high (0.8%) P diet for 2 mo. PTG weight and serum PTH were similar in both groups of normal rats and in uremic rats fed the 0.2% P diet. In contrast, there were significant increases in serum PTH (130 +/- 25 vs. 35 +/- 3.5 pg/ml, P < 0.01), PTG weight (1.80 +/- 0.13 vs. 0.88 +/- 0.06 microg/gram of body weight, P < 0.01), and PTG DNA (1.63 +/- 0.24 vs. 0.94 +/- 0.07 microg DNA/gland, P < 0.01) in the uremic rats fed the 0.8% P diet as compared with uremic rats fed the 0.2% P diet. Serum ICa and 1,25-(OH)2D3 were not altered over this range of dietary P, suggesting a direct effect of P on PTG function. We tested this possibility in organ cultures of rat PTGs. While PTH secretion was acutely (30 min) regulated by medium calcium, the effects of medium P were not evident until 3 h. During a 6-h incubation, PTH accumulation was significantly greater in the 2.8 mM P medium than in the 0.2 mM P medium (1,706 +/- 215 vs. 1,033 +/- 209 pg/microg DNA, P < 0.02); the medium ICa was 1.25 mM in both conditions. Medium P did not alter PTH mRNA in this system, but cycloheximide (10 microg/ml) abolished the effect of P on PTH secretion. Thus, the effect of P is posttranscriptional, affecting PTH at a translational or posttranslational step. Collectively, these in vivo and in vitro results demonstrate a direct action of P on PTG function that is independent of ICa and 1,25-(OH)2D3.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Analysis of Variance
  • Animals
  • Blood Urea Nitrogen
  • Calcium / pharmacology
  • Cattle
  • Cells, Cultured
  • Creatinine / blood
  • Female
  • Humans
  • Hyperplasia
  • Nephrectomy
  • Organ Size
  • Parathyroid Glands / drug effects
  • Parathyroid Glands / growth & development
  • Parathyroid Glands / physiology*
  • Parathyroid Hormone / blood
  • Parathyroid Hormone / metabolism*
  • Phosphorus / deficiency*
  • Phosphorus / pharmacology
  • RNA, Messenger / analysis
  • RNA, Messenger / biosynthesis
  • Rats
  • Rats, Sprague-Dawley
  • Reference Values
  • Regression Analysis
  • Transcription, Genetic / drug effects
  • Uremia / blood
  • Uremia / physiopathology*


  • Parathyroid Hormone
  • RNA, Messenger
  • Phosphorus
  • Creatinine
  • Calcium