The Role of the Hippocampus in Feedback Regulation of the Hypothalamic-Pituitary-Adrenocortical Axis*
Abstract
There is considerable, although not entirely consistent, evidence that the hippocampus inhibits most aspects of HPA activity, including basal (circadian nadir) and circadian peak secretion as well as the onset and termination of responses to stress. Although much of the evidence for these effects rests only on the measurement of corticosteroids, recent lesion and implant studies indicate that the hippocampus regulates adrenocortical activity at the hypothalamic level, via the expression and secretion of ACTH secretagogues. Such inhibition results largely from the mediation of corticosteroid feedback, although more work is required to determine whether the hippocampus supplies a tonic inhibitory input in the absence of corticosteroids. It must be noted that the hippocampus is not the only feedback site in the adrenocortical system, since removal of its input only reduces, but does not abolish, the efficacy of corticosteroid inhibition, and since other elements of the axis appear eventually to compensate for deficits in feedback regulation. The importance of other feedback sites is further suggested not only by the presence of corticosteroid receptors in other parts of the brain and pituitary, but also by the improved prediction of CRF levels by combined hypothalamic and hippocampal receptor occupancy. The likelihood of feedback mediated by nonhippocampal sites underscores the need for future work to characterize hippocampal influence on HPA activity in the absence of changes i…
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Levels of glucocorticoids are regulated via negative feedback loops at several levels of the axis including the hippocampus and PFC.
“levels of glucocorticoids are regulated via negative feedback loops at several levels of the axis including the hippocampus and PFC (Diorio et al., 1993, Jacobson and Sapolsky, 1991).”
From The impact of developmental timing for stress and recovery (2015) · cites this paper as Jacobson and Sapolsky, 1991
GC measures can be an accurate indicator of stress response in vertebrates, once basal and stress-response measures can be differentiated.
“Thus, GC measures can be an accurate indicator of stress response in vertebrates, once basal and stress-response measures can be differentiated (Jacobson and Sapolsky, 1991).”
From Glutamate receptors in domestication and modern human evolution (2020) · cites this paper as Jacobson and Sapolsky, 1991
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Decreased hippocampal volume in healthy girls at risk of depression
Chen, M. C., Hamilton, J. P., & Gotlib, I. H. (2010) · Archives of General Psychiatry · doi:10.1001/archgenpsychiatry.2009.202 · Cited by 220 · see citing works
- Authors
- JACOBSON, L., & SAPOLSKY, R.
- Affiliations
- Stanford University (US)
- Corresponding author
- JACOBSON, LAUREN
- Venue
- Endocrine Reviews
- Publisher
- The Endocrine Society
- Published
- 1991-05
- Volume
- 12
- Issue
- 2
- Pages
- 118-134
- ISSN
- 0163-769X (ISSN-L)
- 1945-7189
- OpenAlex
- W2060644077
- Cited by
- 1,739
- References
- 0
- Citations by year
- 2026: 24 · 2025: 22 · 2024: 59 · 2023: 46 · 2022: 63 · 2021: 44 · 2020: 59 · 2019: 45 · 2018: 43 · 2017: 68 · 2016: 55 · 2015: 62 · 2014: 59 · 2013: 67 · 2012: 70
- FWCI
- 12.62
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Endocrine Reviews (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (5r01ag006633-08, 5f32mh009796-02)
- National Institute on Aging (AG-06633)
- National Institute of Mental Health (MH-09796)
- Topics
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adrenal Hormones and Disorders
- Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
- Keywords
- hippocampus, hypothalamic-pituitary-adrenal axis, corticosteroid feedback, corticosteroid receptors, circadian rhythm, stress response, vasopressin, corticotropin-releasing factor, adrenocortical function, lesion studies, receptor occupancy
- MeSH terms
- Adrenal Cortex, Aging, Animals, Mental Disorders, Feedback, Hippocampus, Humans, Hypothalamus, Pituitary Gland
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