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

被引:390
作者
Slatopolsky, E [1 ]
Finch, J [1 ]
Denda, M [1 ]
Ritter, C [1 ]
Zhong, M [1 ]
Dusso, A [1 ]
MacDonald, PN [1 ]
Brown, AJ [1 ]
机构
[1] ST LOUIS UNIV,SCH MED,DEPT PHARMACOL & PHYSIOL,ST LOUIS,MO 63103
关键词
phosphorus; hyperparathyroidism; calcitriol; calcium; uremia;
D O I
10.1172/JCI118701
中图分类号
R-3 [医学研究方法]; R3 [基础医学];
学科分类号
1001 ;
摘要
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)(2)D-3, whereas in advanced renal failure, P restriction can act independent of changes in 1,25-(OH)(2)D-3 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 mu g/gram of body weight, P < 0.01), and PTG DNA (1.63+/-0.24 vs. 0.94+/-0.07 mu 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)(2)D-3 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/mu g 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 mu g/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)(2)D-3.
引用
收藏
页码:2534 / 2540
页数:7
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