Habener J F
Ciba Found Symp. 1976;41:197-224. doi: 10.1002/9780470720233.ch11.
New information has elucidated many of the biochemical pathways in the formation, release and metabolism of parathyroid hormone (PTH). The hormone is biosynthesized in the parathyroid cells from two distinct precursors, or prohormones, that are modified by specific enzymic cleavages during the synthesis and intracellular transport of the hormonal polypeptide. Release of the hormone from the gland inversely depends on the extracellular calcium concentration, but is regulated over a much narrower range of calcium concentration than was realized previously. This new information points to a pattern of regulation that is more appropriate for homeostasis than was the pattern indicated by earlier studies. The persistence of a basal level of PTH secretion, despite sustained hypercalcaemia, suggests a possible mechanism for the abnormal secretion seen in states of hyperparathyroidism. The discovery of a calium-dependent degradative pathway for PTH in the parathyroid cell indicates that changes in the turnover of PTH may be one means by which calcium regulates the amount of hormone available for secretion. Of the multiple immunoreactive forms of PTH present in the circulation of man and animals, the predominant form in blood appears to be a large biologically-inactive fragment consisting of the middle and carboxy two-thirds of the hormone sequence. At times, smaller biologically-active fragments of PTH may also appear in blood. Most circulating fragments of PTH probably arise from peripheral cleavage of the intact, secreted hormone in kidney and liver, but some forms of the hormone, including prohormones, may also be secreted from the parathyroid gland. The heterogeneity of circulating PTH and the concomitant uncertainties regarding its precise character have introduced difficulties in the interpretation of immunoassay measurements. A further delineation of the pathways and regulation of PTH biosynthesis, secretion and metabolism should lead to the development of more-specific immuno-assays and result in improved diagnosis and management of patients with disorders of the parathyroid glands.
新的信息阐明了甲状旁腺激素（PTH）形成、释放和代谢过程中的许多生化途径。该激素在甲状旁腺细胞中由两种不同的前体或前激素生物合成，在激素多肽的合成和细胞内运输过程中，它们通过特定的酶切作用进行修饰。激素从腺体的释放与细胞外钙浓度呈负相关，但在比以前认识到的更窄的钙浓度范围内受到调节。这一新信息表明了一种比早期研究所指出的模式更适合内环境稳态的调节模式。尽管持续高钙血症，但PTH分泌仍维持基础水平，这提示了甲状旁腺功能亢进状态下异常分泌的一种可能机制。在甲状旁腺细胞中发现PTH的钙依赖性降解途径表明，PTH周转率的变化可能是钙调节可用于分泌的激素量的一种方式。在人和动物循环中存在的多种PTH免疫反应形式中，血液中的主要形式似乎是一种由激素序列中间和羧基三分之二组成的大的无生物活性片段。有时，PTH的较小生物活性片段也可能出现在血液中。大多数循环中的PTH片段可能来自肾脏和肝脏中完整分泌激素的外周裂解，但某些形式的激素，包括前激素，也可能从甲状旁腺分泌。循环中PTH的异质性以及关于其确切性质的相关不确定性给免疫测定结果的解释带来了困难。对PTH生物合成、分泌和代谢途径及调节的进一步阐明应会导致更特异的免疫测定方法的开发，并改善甲状旁腺疾病患者的诊断和管理。
