Calcium-dependent intracellular degradation of parathyroid hormone: a possible mechanism for the regulation of hormone stores.
Calcium-dependent intracellular degradation of parathyroid hormone: a possible mechanism for the regulation of hormone stores.
复制标题
甲状旁腺激素的钙依赖性细胞内降解：激素储存调节的可能机制。
作者：
J. Habener;Byron Kemper;John T. Potts
本文研究了体外牛甲状旁腺切片中甲状旁腺激素（PTH）的生物合成、储存和分泌对细胞外钙离子浓度变化的响应。激素的生物合成进行了评估，通过使用聚丙烯酰胺凝胶电泳，以测量掺入新合成的甲状旁腺激素和甲状旁腺激素（ProPTH）在短（35分钟）孵育。通过对组织和培养基提取物中的[3H]PTH进行电泳分析，确定组织切片中储存和分泌的新合成PTH的量。通过特异性放射免疫测定法测量切片和培养基中的总PTH和ProPTH。当钙从2mM降低到1mM时，PTH分泌率变化5倍。尽管高浓度的钙（5 mM），一些PTH的分泌仍在继续。ProPTH的生物合成只有轻微的变化，ProPTH向PTH的转化与细胞外钙离子浓度无关。甲状旁腺切片在含有大量钙的培养基中孵育期间，PTH的组织储存增加。然而，储存量的增加远小于分泌明显抑制和PTH生物合成速率变化不大的结果所预测的。在高浓度的钙，大部分（高达50%）的新合成的甲状旁腺激素在组织内降解，而在低浓度的钙，很少（小于10%）的甲状旁腺激素降解。在组织或培养基的提取物中均未发现PTH或ProPTH片段，表明降解通过一般蛋白水解而不是通过有限的特异性内肽酶活性迅速发生。这些数据表明，甲状旁腺细胞含有一个钙敏感的PTH降解途径，这条途径可能参与调节激素的产生和分泌。
The dynamics of parathyroid hormone (PTH) biosynthesis, storage, and secretion in bovine parathyroid slices in vitro in response to alterations in the concentrations of extracellular calcium were studied. Hormone biosynthesis was evaluated by using polyacrylamide gel electrophoresis to measure incorporation of [3H]leucine into newly synthesized PTH and proparathyroid hormone (ProPTH) during short (35 min) incubations. Amounts of newly synthesized PTH stored in and secreted from the tissue slices were determined by electrophoretic analysis of [3H]PTH in extracts of tissue and media. Total PTH and ProPTH is slices and media were measured by specific radioimmunoassays. PTH secretion rates changes 5-fold when calcium was lowered from 2mM to 1mM. Secretion of some PTH continued despite high concentrations of calcium (5 mM). Biosynthesis of ProPTH was changed only slightly, and conversion of ProPTH to PTH was independent of the extracellular calcium concentration. Tissue stores of PTH increased during incubation of parathyroid slices in medium containing high amounts of calcium. The increase in stores was much less, however, than predicted by the findings of marked suppression of secretion and little change in rates of PTH biosynthesis. In high concentrations of calcium, a large fraction (up to 50%) of newly synthesized PTH was degraded within the tissue, whereas in low concentrations of calcium, little (less than 10%) of the PTH was degraded. No fragments of PTH or ProPTH were identified in either extracts of tissue or media, suggesting that degradation occurred rapidly by general proteolysis rather than by limited, specific endopeptidase activity. The data suggest that the parathyroid cell contains a calcium-sensitive degradative pathway for PTH and that this pathway may be involved in the regulation of hormone production and secretion.