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Corticosterone and progesterone differentially regulate HPA axis and neuroimmune responses to stress in male rats.

Authors
  • Hueston, Cara M1
  • Deak, Terrence1
  • 1 Behavioral Neuroscience Program, Department of Psychology, State University of New York at Binghamton, Binghamton, NY, USA.
Type
Published Article
Journal
Stress (Amsterdam, Netherlands)
Publication Date
Jul 01, 2020
Volume
23
Issue
4
Pages
368–385
Identifiers
DOI: 10.1080/10253890.2019.1678025
PMID: 31591928
Source
Medline
Keywords
Language
English
License
Unknown

Abstract

In response to stressor exposure, expression of the inflammatory cytokine interleukin-1β (IL-1) is increased within the paraventricular nucleus of the hypothalamus (PVN). Surgical removal of the adrenal glands (ADX) potentiated stress-induced IL-1 expression, suggesting a role for adrenal-derived hormones in constraining stress-evoked increases in IL-1. While corticosterone (CORT) is a primary factor inhibiting IL-1 expression, progesterone (PROG) is also released by the adrenal glands in male rats in response to stress and also has potent anti-inflammatory properties. This series of studies first established doses of CORT and PROG that adequately recapitulate the normal stress-induced rise, and then tested for individual and combined roles of CORT and PROG in mitigating stress-induced expression of inflammatory genes. We found that CORT injection alone attenuated ADX-induced increases in IL-1 expression and normalized the HPA axis response to stress. In general, PROG replacement had little effect on changes in HPA axis responsivity or stress-induced inflammatory measures. When CORT and PROG were co-administered, a small effect on expression of the decoy receptor, IL-1R2 was observed, suggestive of an anti-inflammatory response. Overall, these results suggest that although CORT is likely to be the primary stress-related hormone responsible for constraining cytokine expression evoked by stress, CORT and PROG may exert certain combined actions that temper stress-induced neuroinflammation.LAY SUMMARYExposure to stress promoted expression of inflammation-related genes in the PVN and BNST. This inflammation was mainly suppressed by the adrenal hormone corticosterone, whereas progesterone had a smaller role in mitigating post-stress inflammation.

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