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Circadian Regulation of the Timing of Pre-Ovulatory Luteinizing Hormone Surge in Mice and Hamsters

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Abstract
Endogenous daily (circadian) oscillators ensure the proper timing of physiological and behavioral processes that are essential to health. A set of core clock genes and their protein products function in transcriptional/translational feedback loops (TTFLs) that time and coordinate vital homeostatic, cognitive, and hormonal processes. A master pacemaker in the suprachiasmatic nucleus (SCN) coordinates circadian function throughout the organism. Investigating the causal role of genetically defined cell types in the suprachiasmatic nucleus for circadian rhythms is essential to understand how an animal’s physiology is temporally organized. This thesis explores the role of molecular clocks within particular cell types in regulating physiology. This characterization spans the spectrum from behavior/physiology at the organismal level to characterizing circadian function at the tissue/cell level. Chapter 1 provides a basic overview of circadian rhythms and how they regulate physiology and sets the stage for subsequent sections. In Chapter 2, I describe experiments we performed using conditional mouse models lacking clock function within a circuit that regulates the Luteinizing Hormone (LH) surge. I showed that circadian function within multiple cell types is necessary for the proper timing of LH surge. In Chapter 3, I report on the efforts to determine whether duper alters autonomous clock mechanism (the TTFL) or whether duper alters intercellular coupling of circadian oscillators within the SCN. In Chapter 4, I extend the characterization of the effects of a novel, spontaneous circadian mutation, duper, on the pre-ovulatory LH surge. I conclude by proposing a model to explain shifting of phase in a multioscillatory circuit.
Type
dissertation
Date
2020-09
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http://creativecommons.org/licenses/by/4.0/
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