Phosphorus restriction prevents parathyroid gland growth - High phosphorus directly stimulates PTH secretion in vitro
Phosphorus restriction prevents parathyroid gland growth - High phosphorus directly stimulates PTH secretion in vitro
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DOI：
10.1172/jci118701
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发表时间：
1996-06-01
影响因子：
15.9
通讯作者：
Brown, AJ
中科院分区：
文献类型：
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作者：
Slatopolsky, E;Finch, J;Brown, AJ
在早期肾功能衰竭中，这种作用可能是通过增加1，25-（OH）（2）D-3介导的，而在晚期肾功能衰竭中，限制磷的作用不依赖于1，25-（OH）（2）D-3和血清离子钙（伊卡）的变化。本研究观察了低磷（0.2%）和高磷（0.8%）饲料喂养尿毒症大鼠2个月后，饲料磷对血清甲状旁腺激素（PTH）、PTH mRNA和甲状旁腺增生的影响。PTG重量和血清PTH在正常大鼠和尿毒症大鼠喂养的0.2%P饮食的两组相似。与此相反，（130+/-25 vs，35+/-3.5 pg/ml，P < 0.01），PTG重量（1.80+/-0.13vs，0.88 +/-0.06 μ g/g体重，P < 0.01），PTG DNA（1.63+/-0.24vs.0.94 +/-0.07 μ g DNA/腺体，P < 0.01），与喂食0.2%P饮食的尿毒症大鼠相比，25-（OH）（2）D-3在此范围内没有改变，提示P对PTG功能的直接影响。我们在大鼠PTG器官培养中测试了这种可能性。虽然PTH分泌受培养基钙的急性（30分钟）调节，但培养基P的作用直到3小时才明显。在6小时的孵育期间，PTH在2.8 mM P培养基中的积累显著大于在0.2 mM P培养基中的积累（1，706 +/-215 vs，1，033 +/-209 pg/mug DNA，P < 0.02）;在两种条件下，培养基伊卡均为1.25 mM。在该系统中，培养基P不改变PTH mRNA，但放线菌酮（10 μ g/ml）消除了P对PTH分泌的作用。因此，P的作用是转录后的，在翻译或翻译后步骤影响PTH。总之，这些体内和体外结果表明，P对PTG功能的直接作用不依赖于伊卡和1，25-（OH）（2）D-3。
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.