Physiological Implications of Pulsatile Hormone Secretion
Physiological Implications of Pulsatile Hormone Secretion
复制标题
脉动激素分泌的生理意义
DOI：
10.1111/j.1749-6632.1991.tb27235.x
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发表时间：
1991
影响因子：
5.2
通讯作者：
D. Matthews
中科院分区：
文献类型：
--
作者：
D. Matthews
长期以来，激素的脉动分泌一直是内分泌学家试图定义正常范围和偏离正常范围的一个问题。过去，脉动被视为对试图建立正常范围和病理偏差的内分泌学家来说是一个麻烦。同样，药理学家常常将体内药物的波动视为需要克服的障碍。但并非所有药物都具有相同的属性，尽管在某些治疗情况下波动浓度仍然是一个困难，但在其他情况下，脉动对于治疗的成功结果是有益的，甚至是必需的。对药物类型的大致分类可以澄清和强调这些可能根本不同的不同治疗目标（表 I）。抗生素需要达到所有细菌都会死亡的浓度，并且亚毒性水平持续任何时间都会诱发耐药菌株。只要感染持续存在，水平就需要维持在远高于 ED50 的水平。对于其他物质（例如维生素），可能不需要任何特定的剂量水平或时间关系——“足够”就足够了；身体有足够的能力来缓冲短缺并储存过剩。但第三个主要类别是需要以特定时间模式传递的激素，这些将在下面讨论。通过检查化学信号（激素）的时间生物学属性，发现它们是在豆类中分泌的。这些脉冲现已被描述为胰岛素、谷氨酸激动剂、生长激素、C肽、9.o生长激素（GH）、“*'*皮质醇、'~黄体生成素（LH）、l4.lS促甲状腺激素刺激激素（TSH）、I6和催乳素。”事实上，振荡分泌现象在动物生理学中如此广泛存在，以至于它可以被视为一个基本原理。 I8 内分泌系统的脉动性质是如此重要或如此有效或如此经济或如此敏感，以至于进化决定激素应优先采用这种信号传导方法。为什么会这样呢？一些新出现的原理和见解表明，搏动性可能是内分泌学最重要的特征之一。这里使用胰岛素分泌作为所涉及的一些机制的例子，但是许多结论可以通过类推应用于其他系统。
Pulsatile secretion of hormones has long been a problem to endocrinologists attempting to define normality and deviations from normality.'In the past pulsatility was seen as a nuisance to the endocrinologist trying to establish normal ranges and pathological deviations. Similarly pharmacologists often regarded the fluctuations of drugs within the body as a obstacle to be overcome. But not all drugs have the same attributes, and although fluctuating concentrations are still a difficulty in some therapeutic situations, there are other occasions when pulsatility is beneficial or even mandatory for successful outcome of treatment. An approximate classification of types of drugs can clarify and highlight these different therapeutic aims (TABLE I), which may differ radically. Antibiotics are needed in concentrations such that all bacteria will die, and subtoxic levels persisting for any length of time will induce resistant strains. Levels need to be maintained well above the ED5o for as long as an infection persists.? For other substances (eg, vitamins), there is probably no necessity for any particular dose level or time relationship-" enough" is all that is needed; the body has sufficient capacity to buffer shortages and to store an excess. But a third major category is that of hormones which need to be delivered with specific temporal patterns, and these are discussed below.Examining chemical signals (hormones) for their chronobiological attributes, it emerges that they are secreted in pulses. These pulses have now been described for in~ ulin,~,~ glu~ agon,~.~ somato~ tatin,~.~ C-peptide, 9.'o growth hormone (GH),"*'* corti~ ol,'~ luteinizing hormone (LH), l4. lS thyrotropin stimulating hormone (TSH), I6 and prolactin." Indeed, the phenomenon of oscillatory secretion is so widely found in animal physiology that it can be regarded as a fundamental principle. I8 The pulsatile nature of the endocrine system is so important or so efficient or so economical or so sensitive that evolution has dictated that hormones should preferentially adopt this method of signaling. Why should this be so? There are emerging principles and insights that reflect that pulsatility may be one of the most important features of endocrinology. Insulin secretion is used here as an example of some of the mechanisms involved, but many of the conclusions can be applied, by analogy, to other systems.