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DAILY VARIATIONS OF THE HYPOTHALAMO-PITUITARY-ADRENAL AXIS IN
RESPONSE TO PHYSIOLOGICAL STRESSORS
by
Lori Marie Gorton
A Dissertation Presented to the
FACULTY OF THE GRADUATE SCHOOL
UNIVERSITY OF SOUTHERN CALIFORNIA
In Partial Fulfillment of the
Requirements for the Degree
DOCTOR OF PHILOSOPHY
(NEUROSCIENCE)
December 2007
Copyright 2007 Lori Marie Gorton
Object Description
| Title | Daily variations of the hypothalamo-pituitary-adrenal axis in response to physiological stressors |
| Author | Gorton, Lori Marie |
| Author email | lgorton@usc.edu |
| Degree | Doctor of Philosophy |
| Document type | Dissertation |
| Degree program | Neuroscience |
| School | College of Letters, Arts and Sciences |
| Date defended/completed | 2007-10-05 |
| Date submitted | 2007 |
| Restricted until | Unrestricted |
| Date published | 2007-11-15 |
| Advisor (committee chair) | Watts, Alan |
| Advisor (committee member) |
Swanson, Larry Wood, Ruth Quick, Michael Donovan, Casey |
| Abstract | The pituitary and adrenal gland respond to daytime restricted feeding schedules, but little is known about Crh gene responses. In Chapter 2, we explore the feeding behavior, and levels of CRH hnRNA in the PVH and CRH mRNA in the central nucleus of the amygdala (CEA) in response to 6 hours of daytime restricted feeding. We show that feeding responses are different among feeding groups but there is no change in 24-hour body weight. Also, the significant daily rhythm in Crh gene transcription is lost in animals fed only one meal during the daytime. Remarkably, there is a daily rhythm in CRH mRNA in the CEA of ad lib fed animals that is shifted 180º when food accessibility is daytime restricted.; In Chapters 3 and 4, we determine how the time of day influences the magnitude of adrenocorticotropic hormone (ACTH) and corticosterone responses to hypoglycemia. Little is known about the mechanisms that impart time-of-day differences on neuroendocrine CRH neurons in the hypothalamic paraventricular nucleus (PVH). Rats received 0-3U/kg of insulin (or 0.9% saline) to achieve a range of glucose nadir concentrations. Brains were processed to identify phosphorylated extracellular regulated 1/2 kinases (phospho-ERK1/2)-immunoreactive cells in the PVH and hindbrain and corticotropin-releasing hormone (CRH) heteronuclear (hn) RNA in the PVH. Hypoglycemia did not stimulate ACTH and corticosterone responses in animals unless a glucose concentration of approximately 3.15mM or below was reached. Critically, the glycemic thresholds required to stimulate ACTH and corticosterone release in the morning and night were indistinguishable. Yet, glucose concentrations below the estimated glycemic threshold correlated with a greater increase in corticosterone, ACTH, and phospho-ERK1/2-immunoreactive neurons in the PVH at night compared to morning. In these same animals, the number of phospho-ERK1/2-immunoreactive neurons in the medial part of the nucleus of the solitary tract was unchanged at both times of day. These data collectively support a model whereby changes in forebrain mechanisms alter the sensitivity of neuroendocrine CRH to the hypoglycemia-related information conveyed by ascending catecholaminergic afferents. Circadian clock driven processes in the forebrain would seem to be strong contenders for mediating these effects. |
| Keyword | HPA axis; circadian; hypoglycemia; corticotropin releasing hormone; glucocorticoid; pERK1/2 |
| Language | English |
| Part of collection | University of Southern California dissertations and theses |
| Publisher (of the original version) | University of Southern California |
| Place of publication (of the original version) | Los Angeles, California |
| Publisher (of the digital version) | University of Southern California. Libraries |
| Type | texts |
| Legacy record ID | usctheses-m925 |
| Rights | Gorton, Lori Marie |
| Repository name | Libraries, University of Southern California |
| Repository address | Los Angeles, California |
| Repository email | http://www.usc.edu/isd/libraries/services/ask_a_librarian/email/ |
| Filename | etd-Gorton-20071115 |
| Archival file | uscthesesreloadpub_Volume62/etd-Gorton-20071115.pdf |
Description
| Title | Page 1 |
| Full text | DAILY VARIATIONS OF THE HYPOTHALAMO-PITUITARY-ADRENAL AXIS IN RESPONSE TO PHYSIOLOGICAL STRESSORS by Lori Marie Gorton A Dissertation Presented to the FACULTY OF THE GRADUATE SCHOOL UNIVERSITY OF SOUTHERN CALIFORNIA In Partial Fulfillment of the Requirements for the Degree DOCTOR OF PHILOSOPHY (NEUROSCIENCE) December 2007 Copyright 2007 Lori Marie Gorton |
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