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Home / Equine Research Bank / Endocrinology / Quantifying nonlinear interactions within the hypothalamo-pi...
Endocrinology2008; 150(4); 1941-1951; doi: 10.1210/en.2008-1249

Quantifying nonlinear interactions within the hypothalamo-pituitary-adrenal axis in the conscious horse.

Abstract: Cortisol is an important mediator of physiological stress responses. Hypothalamic CRH and arginine vasopressin (AVP) and pituitary ACTH, in addition to hypothalamic and pituitary cortisol feedback, regulate cortisol secretion. Importantly, joint interactions among the four, rather than the signal of any one hormone, govern this life-preserving axis. Quantifying in vivo strength of such joint interactions has been difficult, especially without direct injection of cortisol, CRH, AVP, or ACTH. The goal of the present research was to estimate these joint feedback and feedforward interactions in vivo in the conscious horse during low-cortisol and hypoglycemic stress. Pituitary venous sampling of ACTH, CRH, and AVP was performed every 0.5-1 min and jugular venous sampling of cortisol every 15-20 min. Estimation of hypothalamic dynamics revealed that: 1) hypocortisolemia amplifies CRH and AVP secretion, when mean (slow) and rate-adjusted (rapid) cortisol feedback concentrations decrease by 0-25%; and 2) reduced peptide feedback augments CRH and AVP secretion, when CRH and AVP secretion each decreases by 0-25 and 50% of its respective maximum. Thus, low-cortisol feedback enhances CRH outflow in part by relieving CRH's autoinhibition. Estimation of pituitary dynamics disclosed that: 1) endogenous CRH and AVP synergize in evoking ACTH secretion, and 2) hypocortisolemia potentiates individual and conjoint stimulation of ACTH secretion by CRH and AVP. Formulations such as the present one should have application to evaluating other complex endocrine dynamics.
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Publication Date: 2008-11-20 PubMed ID: 19022882PubMed Central: PMC2659283DOI: 10.1210/en.2008-1249Google Scholar: Lookup
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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 investigates the complex feedback and feedforward interactions in the hypothalamo-pituitary-adrenal axis in horses under stress conditions. Researchers aim to quantify these interactions, particularly how cortisol, CRH, AVP, and ACTH hormones regulate each other without direct injections.

Objective and Methodology

  • The study’s primary purpose is to quantify the collective interactions among four key hormones (cortisol, CRH, AVP, and ACTH) that participate in the body’s stress response mechanism, particularly in low cortisol and stress-induced hypoglycaemia conditions in conscious horses.
  • Researchers tapped into pituitary venous sampling technique every 0.5-1 minute to measure ACTH, CRH, and AVP hormone levels, and jugular venous sampling method every 15-20 minutes for cortisol level monitoring. This non-invasive approach allowed researchers to observe in vivo dynamics without resorting to hormone injections that may potentially interfere with the body’s natural regulatory mechanism.

Observations & Findings

Hypothalamic Dynamics

  • The study found that when cortisol feedback concentrations decrease by 0-25%, it amplifies the secretion of CRH and AVP – a condition termed as hypocortisolemia. This indicates that low-cortisol feedback enhances CRH release partly by off-setting CRH’s autoinhibition.
  • Also, reduced peptide feedback (i.e., the decrease in CRH and AVP secretion each by 0-25% and 50% of their respective maximum) elevates CRH and AVP release. This shows the complementary dynamics of these hormones in managing stress responses.

Pituitary Dynamics

  • The research revealed that endogenous CRH and AVP act synergistically in prompting ACTH secretion. This shows a level of collaboration among these hormones in forming stress responses.
  • The study also found that hypocortisolemia—characterized by lowered cortisol levels—increases the individual and combined stimulation of ACTH secretion by CRH and AVP. This assertion implies that in conditions of low cortisol, CRH and AVP play a more active role in inducing ACTH and subsequently the stress response.

Implications

  • This research provides insights into managing stress-induced hormonal responses – not just in horses but potentially in other species.
  • Understanding these intricate hormonal dynamics might lead to improved stress and cortisol-related disorders management methods.
  • This study’s methodology could potentially be applied to evaluate other complex endocrine dynamics thereby expanding its relevance to other fields.

Cite This Article

APA
Keenan DM, Alexander S, Irvine C, Veldhuis JD. (2008). Quantifying nonlinear interactions within the hypothalamo-pituitary-adrenal axis in the conscious horse. Endocrinology, 150(4), 1941-1951. https://doi.org/10.1210/en.2008-1249

Publication

Endocrinology
ISSN: 1945-7170
NlmUniqueID: 0375040
Country: United States
Language: English
Volume: 150
Issue: 4
Pages: 1941-1951

Researcher Affiliations

Keenan, Daniel M
  • Department of Statistics, University of Virginia, Charlottesville, Virginia 22904, USA.
Alexander, Sue
    Irvine, Clifford
      Veldhuis, Johannes D

        MeSH Terms

        • Adrenocorticotropic Hormone / metabolism
        • Animals
        • Arginine Vasopressin / metabolism
        • Corticotropin-Releasing Hormone / metabolism
        • Horses
        • Hydrocortisone / metabolism
        • Hypothalamo-Hypophyseal System / metabolism
        • Linear Models
        • Pituitary-Adrenal System / metabolism
        • Radioimmunoassay

        Grant Funding

        • 1UL1RR024150 / NCRR NIH HHS
        • R21 NIA AG029215 / NIA NIH HHS
        • R21 AG029215 / NIA NIH HHS
        • DK073148 / NIDDK NIH HHS
        • UL1 RR024150 / NCRR NIH HHS
        • R01 DK073148 / NIDDK NIH HHS

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