Stress-Induced Sensitization of the Hypothalamic-Pituitary Adrenal Axis Is Associated with Alterations of Hypothalamic and Pituitary Gene Expression
Abstract
We have previously reported that inescapable tail shock (IS) produces persistent changes in hypothalamic-pituitary-adrenal (HPA) axis function. These changes are manifest as an elevation in basal corticosterone (CORT) levels, a sensitization of adrenocorticotropin hormone (ACTH) and CORT responses to subsequent challenge, and a failure of dexamethasone to suppress both the ACTH and CORT responses to a subsequent challenge. The experiments presented here examine IS-induced alterations in the responsiveness of the HPA axis, particularly at the level of the anterior pituitary. The data presented show that adrenalectomy does not abolish the IS-induced sensitization of the HPA axis, suggesting that the sensitization is not solely caused by a defect in glucocorticoid negative feedback. Analysis of gene expression in the anterior pituitary revealed that IS exposure persistently elevated basal levels of proopiomelanocortin (POMC; the precursor to ACTH) mRNA and sensitized the POMC hnRNA and c-fos mRNA response to a subsequent challenge. Analysis of gene expression in the parvocellular division of the paraventricular nucleus of the hypothalamus (pPVN) after IS exposure revealed that basal levels of corticotropin-releasing hormone (CRH) mature mRNA are elevated and the c-fos mRNA response to a subsequent challenge is enhanced. Finally, a blunted in vitro ACTH response to CRH challenge is observed after IS exposure. These data suggest that the ultimate source of the IS-induced sensitization is not the anterior pituitary and implicate an increased drive on the anterior pituitary from the pPVN.
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Various models of stress activate neurons throughout the brain, including hypothalamus, amygdala, hippocampus and cortex.
“Indeed, various models of stress have been shown to activate neurons throughout the brain, including hypothalamus, amygdala, hippocampus and cortex.72,90, 91, 92, 93, 94, 95”
From Preferential loss of dorsal-hippocampus synapses underlies memory impairments provoked by short, multimodal stress (2014) · cites this paper as [94]
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Stress-induced sensitization: the hypothalamic–pituitary–adrenal axis and beyond
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- Authors
- O’Connor, K. A., Ginsberg, A. B., Maksimova, E., Wieseler Frank, J. L., Johnson, J. D., Spencer, R. L., Campeau, S., Watkins, L. R., & Maier, S. F.
- Affiliations
- University of Colorado Boulder (US)
- Venue
- Neuroendocrinology
- Publisher
- S. Karger AG
- Published
- 2004
- Volume
- 80
- Issue
- 4
- Pages
- 252-263
- ISSN
- 0028-3835 (ISSN-L)
- 1423-0194
- OpenAlex
- W2143991348
- Cited by
- 41
- References
- 55
- Citations by year
- 2024: 1 · 2018: 1 · 2017: 1 · 2016: 2 · 2015: 2 · 2014: 5 · 2012: 3
- FWCI
- 0.94
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Neuroendocrinology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adrenal Hormones and Disorders
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuropeptides and Animal Physiology
- Keywords
- hypothalamic-pituitary-adrenal axis, stress sensitization, corticosterone, ACTH, proopiomelanocortin, c-fos, corticotropin-releasing factor, paraventricular nucleus, anterior pituitary, glucocorticoid negative feedback, adrenalectomy, gene expression, chronic stress
- MeSH terms
- Adrenalectomy, Adrenocorticotropic Hormone, Animals, Cell Count, Corticotropin-Releasing Hormone, Dose-Response Relationship, Drug, Electroshock, Gene Expression Regulation, Hypothalamo-Hypophyseal System, Hypothalamus, Male, Pituitary Gland, Pituitary-Adrenal System, Pro-Opiomelanocortin, RNA, Messenger, Stress, Physiological, Time Factors, Gene Expression, Proto-Oncogene Proteins c-fos, Rats, Sprague-Dawley, In Situ Hybridization, Reverse Transcriptase Polymerase Chain Reaction, Rats
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