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

Eduardo Slatopolsky, Jane Finch, Masashi Denda, Cindy Ritter, Min Zhong, Adriana Dusso, Paul N. MacDonald, Alex J. Brown

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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 μg/gram of body weight, P < 0.01), and PTG DNA (1.63±0.24 vs. 0.94±0.07 n.g 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/μg 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 μg/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.

Original languageEnglish
Pages (from-to)2534-2540
Number of pages7
JournalJournal of Clinical Investigation
Issue number11
StatePublished - Jun 1 1996


  • Calcitriol
  • Calcium
  • Hyperparathyroidism
  • Phosphorus
  • Uremia


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