PERIPHERAL METABOLISM OF [S-35]PARATHYROID HORMONE INVIVO - INFLUENCE OF ALTERATIONS IN CALCIUM AVAILABILITY AND PARATHYROID STATUS
PERIPHERAL METABOLISM OF [S-35]PARATHYROID HORMONE INVIVO - INFLUENCE OF ALTERATIONS IN CALCIUM AVAILABILITY AND PARATHYROID STATUS
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DOI：
10.1677/joe.0.1220237
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发表时间：
1989-07-01
影响因子：
4
通讯作者：
POTTS, JT
中科院分区：
文献类型：
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作者：
BRINGHURST, FR;STERN, AM;POTTS, JT
甲状旁腺激素（PTH）主要通过肝脏和肾脏快速代谢为较小的片段，这些片段被认为是无生物活性的。这种外周代谢在PTH总体作用中的意义尚不清楚。某些体外观察结果表明，在体内代谢过程中会产生循环的生物活性氨基末端PTH片段，当采用高灵敏度测定法时，在体内病理情况下（如肾衰竭和共存的甲状旁腺功能亢进），可以在血液中检测到被认为是氨基末端片段的物质。然而，我们最近报道，给予正常大鼠[32 S]牛PTH（[35 S]bPTH）直接标记在氨基末端甲硫氨酸，然后对提取的[35 S]肽进行高分辨率色谱分析，不会导致血液中出现放射性氨基末端片段，即使连续输注示踪剂至接近生理血浆浓度。我们现在已经采用这些技术来解决关于激素代谢的第二个问题：在代谢扰动期间，如改变钙的可用性或改变促钙激素水平，激素代谢是否会改变？然而，[35 S-Met]PRH（900 Ci/mmol）单独或与[3H.sbd.Pro]bPTH一起代谢，无论是在钙剥夺或甲状腺甲状旁腺切除大鼠中，还是在动物首次给予维生素D中毒或维持高钙摄入时，均未导致激素清除率的改变，也未导致可检测到的循环氨基末端片段。同样，肝脏或肾脏中完整激素的组织定位和特异性裂解模式也未因这些不同的操作而改变。我们的结论是，PTH的外周代谢的调节不施加重要的生理控制循环生物活性PTH的浓度和活性amino-terinal片段的激素不释放到血液中，即使在钙剥夺或低钙血症的情况下。
Parathyroid hormone (PTH) is rapidly metabolized, mainly by liver and kidney, to smaller fragments that are believed to be biologically inactive. The significance of this peripheral metabolism in the overall actions of PTH is unclear. Generation of circulating biologically active amino-terminal PTH fragments during metabolism in vivo has been suggested by certain observations in vitro, and what are believed to be amino-terminal fragments may be detectable in blood under pathological circumstances in vivo (such as renal failure and coexistent hyperparathyroidism) when highly sensitive assays are employed. We recently reported, however, that administration to normal rats of [32S]bovine PTH ([35S]bPTH) directly labelled at amino-terminal methionines, followed by high-resolution chromatographic analysis of extracted [35S]peptides, does not result in appearance of radioactive amino-terminal fragments in blood, even when the tracer is continuously infused to near-physiological plasma concentrations. We have now empolyed these techniques to address a second question regarding hormonal metabolism: is hormonal metabolism modified during metabolic perturbations such as changing calcium availability or altered levels of calciotrophic hormones ?. Metabolism of [35S-Met]PRH (900 Ci/mmol), either alone or together with [3H.sbd.Pro]bPTH, however, did not lead to alterations in the rate of hormonal clearance nor to detectable circulating amino-terminal fragments, either in calcium-deprived or thyroparathyroidectomized rats or when animals were first rendered intoxicated with vitamin D or maintained on a high calcium intake. Likewise, tissue localization and specific cleavage patterns of intact hormone in liver or kidney were all unaltered by these various manoeuvers. We conclude that regulation of peripheral metabolism of PTH does not exert important physiological control over the concentration of circulating biologically active PTH and that active amino-terinal fragments of the hormone are not released into blood even under circumstances of calcium deprivation or hypocalcaemia.