Kalsbeek Andries, Fliers Eric
Department of Endocrinology and Metabolism, G2-133, Academic Medical Center of the University of Amsterdam, The Netherlands.
Handb Exp Pharmacol. 2013(217):185-226. doi: 10.1007/978-3-642-25950-0_8.
The highly coordinated output of the hypothalamic biological clock does not only govern the daily rhythm in sleep/wake (or feeding/fasting) behaviour but also has direct control over many aspects of hormone release. In fact, a significant proportion of our current understanding of the circadian clock has its roots in the study of the intimate connections between the hypothalamic clock and multiple endocrine axes. This chapter will focus on the anatomical connections used by the mammalian biological clock to enforce its endogenous rhythmicity on the rest of the body, using a number of different hormone systems as a representative example. Experimental studies have revealed a highly specialised organisation of the connections between the mammalian circadian clock neurons and neuroendocrine as well as pre-autonomic neurons in the hypothalamus. These complex connections ensure a logical coordination between behavioural, endocrine and metabolic functions that will help the organism adjust to the time of day most efficiently. For example, activation of the orexin system by the hypothalamic biological clock at the start of the active phase not only ensures that we wake up on time but also that our glucose metabolism and cardiovascular system are prepared for this increased activity. Nevertheless, it is very likely that the circadian clock present within the endocrine glands plays a significant role as well, for instance, by altering these glands' sensitivity to specific stimuli throughout the day. In this way the net result of the activity of the hypothalamic and peripheral clocks ensures an optimal endocrine adaptation of the metabolism of the organism to its time-structured environment.
下丘脑生物钟高度协调的输出不仅控制睡眠/觉醒（或进食/禁食）行为的日常节律，还直接控制激素释放的许多方面。事实上，我们目前对昼夜节律钟的很大一部分理解都源于对下丘脑生物钟与多个内分泌轴之间密切联系的研究。本章将以一些不同的激素系统作为代表性例子，重点探讨哺乳动物生物钟用于将其内源性节律强加于身体其他部分的解剖学联系。实验研究揭示了哺乳动物昼夜节律钟神经元与下丘脑神经内分泌以及自主神经前体神经元之间联系的高度专业化组织。这些复杂的联系确保了行为、内分泌和代谢功能之间的逻辑协调，这将有助于生物体最有效地适应一天中的不同时间。例如，在下丘脑生物钟在活跃期开始时激活食欲素系统，不仅能确保我们按时醒来，还能使我们的葡萄糖代谢和心血管系统为这种增加的活动做好准备。然而，内分泌腺内的昼夜节律钟很可能也起着重要作用，例如，通过改变这些腺体在一天中对特定刺激的敏感性。通过这种方式，下丘脑和外周生物钟活动最终确保生物体的新陈代谢能根据其时间结构环境进行最佳的内分泌适应。
