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甲状旁腺激素的分泌与降解作为激素池细胞内成熟度的函数。钙和二丁酰环磷酸腺苷的调节作用。

Secretion and degradation of parathormone as a function of intracellular maturation of hormone pools. Modulation by calcium and dibutyryl cyclic AMP.

作者信息

Morrissey J J, Cohn D V

出版信息

J Cell Biol. 1979 Dec;83(3):521-8. doi: 10.1083/jcb.83.3.521.

Abstract

The biosynthesis, processing, and secretion of parthormone and the effect of calcium on these processes were measured in dispersed porcine parthyroid cells incubated with [(35)S]methionine. Proparathormone was detected at 10 min, the earliest time measured, and was rapidly and apparently quantitatively converted to parathormone. The half-life of the prohomormone pool was 15 min. Secretion of parathormone was detected by 20 min. In pulse-chase experiments there was a period between 20 and 40 min during which the wave of newly-synthesized parathormone was secreted. After 40 min during little additional radioactive hormone was secreted, but dibutyryl cyclic AMP, an agent that can mobilize stored parathormone, when added to the incubation mixtures enhanced radioactive parathormone secretion but only after 60 min, although it increased net hormone secretion as determined by radioimmunoassay to the same extent at all times studied. When the ionized calcium concentration of the medium was lowered, more radioactive hormone was secreted at all times but the effect was greatest on that hormone that was synthesized less than 60 min previously ; however, net hormone secretion in contrast to radioactive hormone was enhanced equally at all intervals. These data could mean that the refractoriness to secretion of parathormone 40-60 min of age was related to maturation of secretory container preparatory to storage. Low calcium (0.5 mM) stimulated hormone secretion up to fivefold compared to high calcium (3.0 mM) but did not affect synthesis of parathormone or proparathormne or conversion of the latter to hormone. During processing at least 70 percent of the intracellular parathormone was lost, presumably through proteolysis and this degradation was greater at high calcium. These data have been interpreted in light of the concept that two secretable pools of parathormone exist within the parathyroid.

摘要

在与[³⁵S]甲硫氨酸一起孵育的分散猪甲状旁腺细胞中,测量了甲状旁腺激素的生物合成、加工和分泌以及钙对这些过程的影响。在最早测量的10分钟时检测到前甲状旁腺激素,并且它迅速且明显定量地转化为甲状旁腺激素。前激素池的半衰期为15分钟。在20分钟时检测到甲状旁腺激素的分泌。在脉冲追踪实验中,在20至40分钟之间有一段时间,在此期间新合成的甲状旁腺激素波被分泌。40分钟后,几乎没有额外的放射性激素被分泌,但是二丁酰环磷酸腺苷(一种可以动员储存的甲状旁腺激素的物质),当添加到孵育混合物中时,尽管在所有研究时间通过放射免疫测定法测定其增加净激素分泌的程度相同,但仅在60分钟后增强了放射性甲状旁腺激素的分泌。当培养基中的离子钙浓度降低时,在所有时间都有更多的放射性激素被分泌,但对在60分钟之前合成的激素影响最大;然而,与放射性激素相反,净激素分泌在所有时间段均同等增强。这些数据可能意味着40 - 60分钟龄的甲状旁腺激素对分泌的不应性与储存前分泌容器的成熟有关。与高钙(3.0 mM)相比,低钙(0.5 mM)刺激激素分泌增加高达五倍,但不影响甲状旁腺激素或前甲状旁腺激素的合成以及后者向激素的转化。在加工过程中,至少70%的细胞内甲状旁腺激素丢失,推测是通过蛋白水解,并且这种降解在高钙时更大。这些数据已根据甲状旁腺内存在两个可分泌的甲状旁腺激素池的概念进行了解释。

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