Glucocorticoid Receptor Density and Binding Affinity in Healthy Horses and Horses with Systemic Inflammatory Response Syndrome

• Published in: Journal of veterinary internal medicine 2015-03, Vol.29 (2), p.626-635
• Main Authors: Hoffman, C.J., McKenzie, H.C., Furr, M.O., Desrochers, A.
• Format: Article
• Language: English
• Subjects: Adrenal glands; Adrenocorticotropic hormone; Adrenocorticotropic Hormone - pharmacology; Affinity; Animals; Cortisol; Critical Illness; Critical illness‐related corticosteroid insufficiency; Density; Equine; Flow Cytometry; Glucocorticoid receptor; Glucocorticoids; Hormones; Horse Diseases - metabolism; Horses; Hydrocortisone - metabolism; Hypothalamic-pituitary-adrenal axis; Hypothalamo-Hypophyseal System - physiology; Hypothalamus; Illnesses; Immunoglobulins; Inflammation; Inflammatory bowel disease; Inflammatory response; Leukocytes, Mononuclear - metabolism; Medical prognosis; Pituitary; Pituitary-Adrenal System - physiology; Protein Binding; Receptor density; Receptors, Glucocorticoid - genetics; Receptors, Glucocorticoid - metabolism; Sepsis; Studies; Systemic inflammatory response syndrome; Systemic Inflammatory Response Syndrome - metabolism; Systemic Inflammatory Response Syndrome - veterinary; Triglycerides
• ISSN: 0891-6640; 1939-1676
• DOI: 10.1111/jvim.12558

Background 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. Animals 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