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

这项研究项目分析了激素昼夜节律控制的功能意义和机制。昼夜节律是由内部机制控制的日常节律，这种机制被称为生物时钟，由外部光周期同步。生物钟存在于身体的许多组织中；我们的论点是，这些组织主要通过荷尔蒙的节律来协调成一个同步的网络。这种网络创造了对生命至关重要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。这项研究使用了一种昆虫Rhodnius prolixus，因为它在激素节律研究中具有许多在高等动物中没有的独特属性。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。我们分析了大脑时钟的复杂神经结构，发现它控制着许多激素有节奏地释放到血液中。这一系统与哺乳动物下丘脑对脑下垂体激素节律的控制密切相关。其中一种荷尔蒙起到了“时间信使”的作用，使位于内分泌腺中的时钟与大脑时钟同步。这是一种荷尔蒙的新功能。这项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(以及直接光敏感度)在相互协调它们以及与大脑时钟协调进入我们设想的计时网络中的作用。我们将分析这些激素以及类固醇和褪黑素对时钟细胞内产生计时的分子振荡器的作用。还有额外的荷尔蒙“时间使者”吗？大脑时钟接收类固醇荷尔蒙节律的“时间反馈”，从而能够进行关于如何将光信号与内部荷尔蒙时间信号相结合的新颖实验。荷尔蒙节律在幼虫和成虫阶段都有发现，睾丸和卵巢都会被检查时钟和荷尔蒙(和光)对它们的作用。这项工作将在理解激素节律如何使细胞和组织相互协调以及与外部世界协调方面取得重大进展。

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.