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Home / Equine Research Bank / J Vet Intern Med / Glucocorticoid receptor density and binding affinity in heal...
Journal of veterinary internal medicine2015; 29(2); 626-635; doi: 10.1111/jvim.12558

Glucocorticoid receptor density and binding affinity in healthy horses and horses with systemic inflammatory response syndrome.

Abstract: Dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis occurs in horses with systemic inflammatory response syndrome (SIRS). Peripheral resistance to glucocorticoids has not been investigated in horses. Objective: To determine if glucocorticoid receptor (GR) function in horses can be measured using flow cytometry, and to use this information to evaluate HPA axis dynamics. Methods: Eleven healthy adult horses in parts 1 and 2. Ten horses with SIRS and 10 age and sex matched controls in part 3. Methods: Flow cytometry was used to evaluate GR density and binding affinity (BA) in 3 healthy horses in part 1. In part 2, exogenous ACTH was administered to eight healthy horses. Their cortisol response and GR properties were measured. In part 3, CBC, serum biochemistry, cortisol and ACTH, and GR properties were compared between controls without SIRS (n = 10) and horses with SIRS (n = 10), and between survivors and nonsurvivors (n = 4 and n = 6 respectively). Results: Flow cytometry can be used to measure GR properties in equine PBMCs. No correlation was observed between plasma cortisol concentration and GR density or BA in healthy horses (r = -0.145, P = .428 and r = 0.046, P = .802 respectively). Nonsurvivors with SIRS had significantly decreased GR BA (P = .008). Horses with triglyceride concentration > 28.5 mg/dL had increased odds of nonsurvival (OR=117; 95% CI, 1.94-7,060). GR BA <35.79% was associated with nonsurvival (OR = 30.33; 95% CI, 0.96-960.5). Conclusions: Tissue resistance to glucocorticoids contributes to HPA axis dysfunction in adult horses with SIRS. These horses might benefit from treatment with exogenous glucocorticoids.
Copyright © 2015 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of the American College of Veterinary Internal Medicine.
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Publication Date: 2015-03-31 PubMed ID: 25818217PubMed Central: PMC4895485DOI: 10.1111/jvim.12558Google Scholar: Lookup
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  • Journal Article

Summary

This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.

This research involves studying the density and binding affinity of glucocorticoid receptors in horses, focusing on healthy horses and those suffering from systemic inflammatory response syndrome (SIRS). The aim is to see whether these factors can shed light on the dynamics of the horse’s hypothalamic-pituitary-adrenal (HPA) axis and the disorder of this system in horses with SIRS.

Methodology

  • The researchers conducted the study in three parts, each involving a different set of horses and objectives.
  • In the first part, three healthy horses were subjected to flow cytometry to evaluate glucocorticoid receptor (GR) density and binding affinity.
  • The second part involved giving eight healthy horses exogenous ACTH (a hormone that stimulates the adrenal glands to release cortisol and other compounds). This was to observe the response of cortisol and GR properties in these horses.
  • In the last part, the researchers compared various parameters such as complete blood count (CBC), serum biochemistry, cortisol and ACTH levels, and GR properties between a group of horses suffering from SIRS and a control group of healthy horses.
  • The same parameters were also compared between survivors and nonsurvivors of SIRS.

Results and Interpretation

  • Flow cytometry was found to be an effective method for examining GR properties in horse immune cells (PBMCs).
  • In healthy horses, no correlation was found between plasma cortisol levels and GR density or binding affinity.
  • Horses that did not survive SIRS demonstrated a significant decrease in GR binding affinity.
  • Horses with triglyceride levels above 28.5 mg/dL had increased odds of not surviving – indicating a potential risk factor for mortality in horses suffering from SIRS.
  • Similarly, a GR binding affinity of less than 35.79% was associated with poor survival outcomes.

Conclusions

  • The study concludes that tissue resistance to glucocorticoids – steroids that reduce inflammation and regulate metabolism – can contribute to HPA axis dysfunction in adult horses with SIRS.
  • This HPA axis dysfunction may be a key factor in the severity of SIRS in horses.
  • The findings suggest that horses suffering from SIRS may benefit from treatment with exogenous glucocorticoids to potentially improve their health outcomes.

Cite This Article

APA
Hoffman CJ, McKenzie HC, Furr MO, Desrochers A. (2015). Glucocorticoid receptor density and binding affinity in healthy horses and horses with systemic inflammatory response syndrome. J Vet Intern Med, 29(2), 626-635. https://doi.org/10.1111/jvim.12558

Publication

Journal of veterinary internal medicine
ISSN: 1939-1676
NlmUniqueID: 8708660
Country: United States
Language: English
Volume: 29
Issue: 2
Pages: 626-635

Researcher Affiliations

Hoffman, C J
  • Marion duPont Scott Equine Medical Center, Virginia/Maryland Regional College of Veterinary Medicine, Leesburg, VA.
McKenzie, H C
    Furr, M O
      Desrochers, A

        MeSH Terms

        • Adrenocorticotropic Hormone / pharmacology
        • Animals
        • Critical Illness
        • Flow Cytometry
        • Horse Diseases / metabolism
        • Horses
        • Hydrocortisone / metabolism
        • Hypothalamo-Hypophyseal System / physiology
        • Leukocytes, Mononuclear / metabolism
        • Pituitary-Adrenal System / physiology
        • Protein Binding
        • Receptors, Glucocorticoid / genetics
        • Receptors, Glucocorticoid / metabolism
        • Systemic Inflammatory Response Syndrome / metabolism
        • Systemic Inflammatory Response Syndrome / veterinary

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        Citations

        This article has been cited 2 times.
        1. Stewart AJ, Hackett E, Bertin FR, Towns TJ. Cortisol and adrenocorticotropic hormone concentrations in horses with systemic inflammatory response syndrome.. J Vet Intern Med 2019 Sep;33(5):2257-2266.
          doi: 10.1111/jvim.15620pubmed: 31512777google scholar: lookup
        2. Sheats MK. A Comparative Review of Equine SIRS, Sepsis, and Neutrophils.. Front Vet Sci 2019;6:69.
          doi: 10.3389/fvets.2019.00069pubmed: 30931316google scholar: lookup
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