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Cited by 666Stress Responses and CortisolAdrenal Hormones and DisordersEstrogen and related hormone effects

Variations in the hypothalamic-pituitary-adrenal response to stress during the estrous cycle in the rat

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VIAU, VICTOR, MEANEY, MICHAEL J.·1991·Endocrinology
DOI 10.1210/endo-129-5-2503
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Abstract

To investigate the role of gonadal steroids in the hypothalamic-pituitary-adrenal (HPA) response to stress, we studied adrenocorticotrophin (ACTH) and corticosterone (B) responses to 20-min restraint stress in cycling female rats, and in ovariectomized (OVX) rats replaced with physiological levels of estradiol (E2) and progesterone (P). In cycling rats, we found significantly higher peak ACTH (P less than 0.01) and B (P less than 0.05) responses to stress during proestrus compared to the estrous and diestrous phases. No differences were found in either basal ACTH and B levels across the cycle phases. In a separate study, OVX rats were maintained on low, physiological levels of E2 and P with silastic implants for 3 days, and injected either with oil (O'), 10 micrograms of E2 (E') 24 h before stress testing, or with E2 and 500 micrograms P 24 and 4 h, respectively, prior to stress (EP'). These treatments mimicked endogenous profiles of E2 and P occurring during diestrous, proestrous, and late proestrous-early estrous phases, respectively. In response to stress, ACTH levels were higher (P less than 0.01) in the E' group compared to the EP' and O' groups. Although the peak B response was similar in all groups, the E' and EP' groups secreted more B after the termination of stress than did the O' group. Within the 20 min stress period, ACTH levels in the E' group were significantly (P less than 0.05) higher at 5, 10, and 15 min after the onset of stress, compared to the EP' and O' groups. Plasma B levels were significantly higher in the E' group at 5 and 10 min (P less than 0.05 and P less than 0.01, respectively) compared to the EP' and O' group. beta-endorphin-like immunoreactive responses to restraint stress were also significantly higher in the E' group compared to the EP' (P less than 0.05) and O' (P less than 0.01) groups. In contrast to the effect seen at 24 h, ACTH responses to stress 48 h after E2 injection in the E' group were comparable to O' animals. There was no effect of E2 on ACTH clearance, whereas B clearance was enhanced in E' treated animals vs. O'-treated animals. These results indicate that the HPA axis in the female rat is most sensitive to stress during proestrous. Such enhanced HPA responses to stress are limited to the early portion of proestrous, as progesterone appears to inhibit the facilitatory effects of estrogen on ACTH release during stress. Taken together, these results suggest an ovarian influence on both activational and inhibitory components of HPA activity.

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Crossref · 10.1210/endo-129-5-2503

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  • Enhanced ACTH secretion on proestrus conflicts with the idea that CRH-BP restricts CRH, suggesting other upstream factors are involved.

    “Thus, these data may indicate that there are other upstream factors involved.”

    From Hypothalamic–pituitary–adrenal and hypothalamic–pituitary–gonadal axes: sex differences in regulation of stress responsivity (2017) · cites this paper as Viau & Meaney, 1991

    The Additional information section reports enhanced stress-induced ACTH secretion during early proestrus and proposes changes in norepinephrine-sensitive adrenergic signaling as a possible upstream influence on CRH release. It does not discuss CRH-binding protein or say that the ACTH response conflicts with a CRH-BP restriction of CRH. (LLM, conf=0.84)

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  • During the estrus phase when E2 levels are lowest, CORT response to stress is reduced compared with proestrus when E2 and P4 levels are elevated.

    “This is further supported by observations that during the estrus phase of the estrous cycle, when E2 levels are lowest, CORT response to stress is reduced compared to during proestrus when E2 and P4 levels are elevated87.”

    From Emerging insights into hypothalamic‐pituitary‐gonadal axis regulation and interaction with stress signalling (2018) · cites this paper as [87]

    The ‘Basal And Stress ACTH And B Levels In Cycling Rats’ section reports a higher corticosterone response to restraint stress in proestrous rats than in estrous rats. The ‘Estrous Cycle’ section says estrogen and progesterone are low during estrous, but progesterone rises later in proestrous; the ‘Additional information’ section says the enhanced stress response appears restricted to early proestrous, when both hormones were not shown to be elevated. The claim therefore supports the response comparison but oversimplifies its hormonal timing. (LLM, conf=0.88)

    Experimental — accuracy not yet measured

  • In female rats, ovariectomy reduces and estradiol treatment increases HPA axis gain.

    “ovariectomy reduces, while estradiol treatment increases, the gain of the HPA axis”

    From Hypothalamic–pituitary–adrenal and hypothalamic–pituitary–gonadal axes: sex differences in regulation of stress responsivity (2017) · cites this paper as Viau & Meaney, 1991

  • In female rats, stress hormone levels are higher on proestrus than on estrus.

    “These hormonal changes correlate with higher stress hormone levels in female rats noted on proestrus when compared to rats that are in estrus, a time when estradiol and progesterone levels are reduced (Viau & Meaney, 1991).”

    From Hypothalamic–pituitary–adrenal and hypothalamic–pituitary–gonadal axes: sex differences in regulation of stress responsivity (2017) · cites this paper as Viau & Meaney, 1991

  • In rats, progesterone and estrogen have been shown to directly impact the stress response in females.

    “In rats, progesterone and estrogen have been shown to directly impact the stress response in females (277).”

    From Epigenetic Modifications in Stress Response Genes Associated With Childhood Trauma (2019) · cites this paper as [277]

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Research works printed but not linked: 4

  1. Baxter ID, Tyrrell lB 1987 The adrenal cortex. In: Felig P, Baxter, ID, Broadus AE, Frohman LA (eds) Endocrinology and Metabolism. 2nd edition. McGraw-Hill, New York, p 511
  2. Erickson OF 1981 The ovary: Basic principles and concepts. In Felig P, Baxter, JO, Broadus AE, l<'rohman LA (eds) Endocrinology and Metabolisrn. 2nd edition. McÙraw- Hill, New York, p 905
  3. Feder HH 1981 E~trous cyclicity in mammals. In: Adler NT (ed) Neuroendocrinology of Reproduction. Plenum Press, New York. p 279
  4. Jones MT, Gillham B, Greenstein BD, Beckford U, Holmes MC 1982 Feedback actions of adrenal steroid honnones. In: Ganten D, Pfaff 0 (eds) CUITent Topies In Neuroendocrinology, Springer, New York, 2: 45

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Authors
VIAU, V., & MEANEY, M. J.
Affiliations
Douglas Mental Health University Institute (CA)
ORCID
Venue
Endocrinology
Publisher
The Endocrine Society
Published
1991-11
Volume
129
Issue
5
Pages
2503-2511
ISSN
  • 0013-7227 (ISSN-L)
  • 1945-7170
DOI
10.1210/endo-129-5-2503
OpenAlex
W2014570372
Cited by
666
References
61
Citations by year
2026: 9 · 2025: 7 · 2024: 9 · 2023: 17 · 2022: 22 · 2021: 16 · 2020: 13 · 2019: 23 · 2018: 11 · 2017: 13 · 2016: 28 · 2015: 10 · 2014: 33 · 2013: 33 · 2012: 13
FWCI
4.15
Type
journal article
Language
en
Open access
Locations
  • Endocrinology (publishedVersion)
  • PubMed (publishedVersion)
  • eScholarship@McGill (McGill) (submittedVersion)
  • Library and Archives Canada (Government of Canada) (submittedVersion)
  • McGill-DEV
Topics
  • Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adrenal Hormones and Disorders
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Estrogen and related hormone effects
Keywords
hypothalamic-pituitary-adrenal axis, estrous cycle, sex steroids, estradiol, progesterone, restraint stress, ACTH, corticosterone, beta-endorphin, ovariectomy, proestrus, stress response, rats, silastic implants
MeSH terms
Adrenocorticotropic Hormone, Animals, Corticosterone, Estradiol, Estrus, Female, Half-Life, Hypothalamo-Hypophyseal System, Ovariectomy, Pituitary-Adrenal System, Rats, Inbred Strains, Stress, Physiological, Rats

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