Time of Day Influences on Gonadotropin Releasing Hormone Neurons
Hickok, Jason Ralph
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Permalink
https://hdl.handle.net/2142/86694
Description
Title
Time of Day Influences on Gonadotropin Releasing Hormone Neurons
Author(s)
Hickok, Jason Ralph
Issue Date
2007
Doctoral Committee Chair(s)
Tischkau, Shelley A.
Department of Study
Microbiology
Discipline
Microbiology
Degree Granting Institution
University of Illinois at Urbana-Champaign
Degree Name
Ph.D.
Degree Level
Dissertation
Keyword(s)
Biology, Cell
Language
eng
Abstract
Gonadotropin Releasing Hormone (GnRH) neurons are typically referred to as the final component of the neuronal network that regulated reproduction. Though it has been known since the 1920's that the decapeptide released by these neuroendocrine cells is the fundamental driver of ovulation in mammalian females, understanding the regulation of its release has been an arduous affair. Neural afferents from all regions of the brain project to these neurons. While stress and nutritional status can alter their function, it is primarily a precisely timed cue of neuronal origin and endocrine status that drive the GnRH neurons to release a bolus of GnRH late on the afternoon of proestrus. Understanding of the timing cue remains ambiguous at best, but circadian input is suspected. My studies found that mouse GnRH neurons express period 2 (Per2) and brain muscle ARNT like protein (Bmal) with a circadian period, and thus likely run a functional molecular clock. Further, vasoactive intestinal peptide (VIP), but not arginine vasopressin (AVP), was capable of synchronizing clock gene oscillations in GT1-7 cells and is likely a part of the precisely timed cue. Microarray studies on GT1-7 cells found numerous receptors with cognate peptides that are expressed in the suprachiasmatic nucleus SCN. A separate but related group of experiments attempted to isolate a pure population of GnRH neurons from GnRH-eGFP transgenic mice by florescence activated cell sorting (FACS) and analyze the mRNA of this population by microarray throughout the course of the day of the luteinizing hormone (LH) surge. Though some success was obtained in development of the isolation procedure, the array experiments were ultimately indicative of the anterior hypothalamus and not GnRH neurons alone. 20k means clustering analysis revealed four clusters of mRNAs that were exhibiting five fold changes at time points just before and after the LH surge. Examination of these clusters found several genes that might be involved in GnRH regulation and implied that cytokines might play a fundamental role in regulating this heavily innervated region.
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