ROLES OF CIRCADIAN CLOCKS IN REGULATION OF THE ENDOCRINE SYSTEM IN AN INSECT

本研究项目分析激素昼夜节律控制的功能意义和机制。昼夜节律是由称为“生物钟”的内部机制控制的日常节奏，生物钟由外部光周期同步。生物钟存在于许多身体组织中；我们的论点是，这些主要是通过激素的节奏协调成一个同步的网络。这个网络创造了生命所必需的细胞和组织的内部组织；它的崩溃，就像人类轮班工人一样，会导致疾病和过早死亡。我们的目标是找出这个组织是如何实现的。这项研究采用了一种昆虫，因为它具有许多在高等动物中没有发现的激素节律研究的独特属性。这些数据适用于所有动物，并将导致医学、农业和病虫害防治方面的进步。所有这些都将使加拿大受益。我们分析了大脑生物钟复杂的神经结构，发现它控制着大量激素有节奏地释放到血液中。这个系统与哺乳动物的下丘脑对垂体激素节律的控制非常相似。其中一种激素充当“时间信使”，使内分泌腺中的时钟与大脑时钟同步。这是激素的一种新型功能。该建议分析了外周组织中的其他时钟，以及各种其他大脑激素（也包括直接光敏感性）在相互协调和与大脑时钟协调中的作用，从而形成我们设想的定时网络。我们将分析这些激素，以及类固醇和褪黑激素对时钟细胞内产生计时的分子振荡器的作用。是否有额外的荷尔蒙“时间信使”？大脑时钟接收来自类固醇激素节律的“时间反馈”，从而可以进行关于如何将光信号与内部激素时间信号相结合的新实验。在幼虫期和成虫期都可以发现激素节律，睾丸和卵巢都将被检查生物钟和激素（以及光线）对它们的作用。这项工作将在理解激素节律如何协调细胞和组织之间以及与外部世界的关系方面取得重大进展。

This research program analyzes the functional significance and mechanisms of control of circadian rhythms in hormones. Circadian rhythms are daily rhythms that are controlled by internal mechanisms called 'biological clocks', which are synchronized by external light cycles. Clocks occur in many body tissues; our thesis is that these are coordinated into a synchronized network mainly by rhythms in hormones. This network creates the internal organization of cells and tissues that is essential for life; its breakdown, as in human shift workers, leads to illness and premature death. Our goal is to find out how this organization is achieved. This research employs an insect Rhodnius prolixus as it has many unique attributes for hormone rhythm studies that are not found in higher animals. The data apply to all animals and will lead to advances in medicine, agriculture and pest control. All these will benefit Canada.We analyzed the complex neural structure of the brain clock and showed it controls rhythmic release of numerous hormones into the blood. This system is closely parallel to the hypothalamic control of pituitary hormone rhythms in mammals. One of these hormones acts as a 'messenger of time' that synchronizes clocks located in endocrine glands with the brain clock. This is a novel type of function for a hormone. This proposal analyzes other clocks in peripheral tissues and the roles of various other brain hormones (and also direct light sensitivity) in coordinating them with each other and with the brain clock, into the timing network that we envisage. We will analyze the actions of these hormones, and also steroids and melatonin on the molecular oscillator within clock cells that generates timekeeping. Are there additional hormonal 'messengers of time'? The brain clock receives 'temporal feedback' from a steroid hormone rhythm, enabling novel experiments on how it integrates light signals with internal hormonal time signals. Hormone rhythms are found in both larval and adult stages, and both testes and ovaries will be examined for clocks and the actions of hormones (and light) on them. The work will produce major advances in understanding how hormone rhythms coordinate cells and tissues both with each other and with the external world.