Repository logo
 

Sex-dependent function and regulation of the hypothalamic pituitary adrenal axis

Simple item page
dc.contributor.authorHeck, Ashley L., author
dc.contributor.authorHanda, Robert, advisor
dc.contributor.authorBouma, Gerrit, committee member
dc.contributor.authorHentges, Shane, committee member
dc.contributor.authorFlorant, Gregory, committee member
dc.date.accessioned2020-01-13T16:42:14Z
dc.date.available2020-01-13T16:42:14Z
dc.date.issued2019
dc.description.abstractPhysiological responses to stressors are largely governed by a neuroendocrine axis, the hypothalamic pituitary adrenal (HPA) axis. Whereas HPA activation is necessary for body wide adaptation to a stressor via the production of glucocorticoids, its excessive or inappropriate activation can increase risk for a number of diseases. Importantly, many of these stress-related diseases exhibit a strong sex bias in prevalence, which may be related to sex differences in the activity of the HPA axis. Thus, the studies described in this dissertation examine sex differences in the regulation and function of the HPA axis in rodents to further unravel the sex-dependent vulnerability often characteristic of stress-related diseases in humans. In Chapters 2 and 3, sex differences in glucocorticoid negative feedback at the level of corticotropin releasing hormone (Crh) in the hypothalamic paraventricular nucleus (PVN), an important factor limiting HPA axis activation, are explored. Results of Chapter 2 indicate that male C57BL/6 mice exhibit a more rapid response of PVN Crh expression to the removal of glucocorticoid negative feedback due to androgen actions, likely via upstream regulatory neurons. Results of Chapter 3, alternatively, show more robust glucocorticoid receptor (GR) mediated negative feedback on PVN Crh in females, but only on a day of their reproductive cycle when circulating estrogen levels are low. Thus, a complex interplay among androgen/ estrogen actions and glucocorticoid regulatory mechanisms appears to drive sex-dependent PVN Crh expression to potentially influence sex-biased HPA activity and stress-related disease risk. In Chapters 4 and 5, the response of the HPA axis to chronic stress, a factor which is more etiologically relevant for human disease risk, is examined. The results of Chapter 4 demonstrate that female C57BL/6 mice exhibit time-of-day dependent changes in the basal and acute stress-induced activity of the HPA axis following chronic variable stress (CVS). Male mice, conversely, appear mostly resistant to the effects of CVS on HPA function until socially isolated (Chapter 5). These findings establish an essential foundation for the use of the C57BL/6 mouse, a strain typically more resistant to the effects of CVS, in future studies of sex-dependent HPA axis regulation following chronic stress.
dc.format.mediumborn digital
dc.format.mediumdoctoral dissertations
dc.identifierHeck_colostate_0053A_15837.pdf
dc.identifier.urihttps://hdl.handle.net/10217/199857
dc.languageEnglish
dc.language.isoeng
dc.publisherColorado State University. Libraries
dc.relation.ispartof2000-2019
dc.rightsCopyright and other restrictions may apply. User is responsible for compliance with all applicable laws. For information about copyright law, please see https://libguides.colostate.edu/copyright.
dc.subjectcorticotropin releasing hormone (CRH)
dc.subjecthypothalamic pituitary adrenal (HPA) axis
dc.subjectchronic variable stress
dc.subjectsex differences
dc.subjectglucocorticoids
dc.titleSex-dependent function and regulation of the hypothalamic pituitary adrenal axis
dc.typeText
dcterms.rights.dplaThis Item is protected by copyright and/or related rights (https://rightsstatements.org/vocab/InC/1.0/). You are free to use this Item in any way that is permitted by the copyright and related rights legislation that applies to your use. For other uses you need to obtain permission from the rights-holder(s).
thesis.degree.disciplineBiomedical Sciences
thesis.degree.grantorColorado State University
thesis.degree.levelDoctoral
thesis.degree.nameDoctor of Philosophy (Ph.D.)

Files

Original bundle
Now showing 1 - 1 of 1
Thumbnail Image
Name:
Heck_colostate_0053A_15837.pdf
Size:
5.88 MB
Format:
Adobe Portable Document Format
Download

Collections

2000-2019
Theses and Dissertations