Free and bound cortisol in plasma and saliva during ACTH challenge in dairy cows and horses.
- Journal Article
Summary
The research article investigates how cortisol levels in dairy cows and horses respond to a standardized activation of their hypothalamic-pituitary-adrenocortical (HPA) axis using synthetic Adrenocorticotropic Hormone (ACTH). It also explores the extent to which saliva cortisol is representative of alterations in plasma-free cortisol and adrenal cortex reactivity.
Objective of the Study
The goal of this study was to establish a method that can assess free cortisol (the form of cortisol that actively regulates metabolic and immunological processes) in cows and horses. This method allows interpretation of the proportional changes of cortisol in saliva and blood in response to a standardized HPA axis activation via synthetic ACTH. The researchers also aimed to determine if the ratios of cortisol fractions at basal levels in healthy horses and dairy cows change during HPA axis activation, and how reliable saliva cortisol (SC) is for presenting alterations in plasma-free cortisol (FC) and adrenal cortex reactivity.
Methodology
- Synthetic ACTH was administered intravenously to eight dairy cows and five horses. The dosages were based on published data.
- For 3 hours, blood and saliva were collected every 30 minutes from a jugular vein catheter. These samples were analyzed for total cortisol (TC) and SC, the ratio of free cortisol (rFC), and the concentration of FC in plasma.
Findings
- All cortisol fractions increased within 30 minutes of ACTH administration compared to basal values (0 minutes).
- Peak TC concentration reached 63.2 ± 9.6 ng/mL in bovine plasma and 73.2 ± 11.8 ng/mL in equine plasma.
- Peak values of rFC averaged 17.9 ± 4.5% in cows and 19.2 ± 7.8% in horses.
- The SC to cFC ratio in horses remained similar throughout the ACTH challenge, indicating that SC is sourced from plasma FC.
- However, SC increased less compared to plasma TC and FC during HPA axis activation in cows.’
Conclusion
The research concluded that the short-term activation of the HPA axis through the administration of ACTH causes elevation of TC and a similar increase of rFC in both species. SC changes closely reflected FC changes in horses, but less accurately in cows. Understanding these changes among cortisol fractions could provide further insight into glucocorticoid regulation adaptation mechanisms and differentiate cortisol-related health disorders.
Cite This Article
Publication
Researcher Affiliations
- Veterinary Physiology, Vetsuisse Faculty, University of Bern, Bern, Switzerland.
- Graduate School for Cellular and Biomedical Sciences, University of Bern, Bern, Switzerland.
- Graduate School for Cellular and Biomedical Sciences, University of Bern, Bern, Switzerland.
- Department of Clinical Veterinary Medicine, Swiss Institute for Equine Medicine (ISME), Vetsuisse Faculty, University of Bern, and Agroscope, Bern, Switzerland.
- Department of Clinical Veterinary Medicine, Swiss Institute for Equine Medicine (ISME), Vetsuisse Faculty, University of Bern, and Agroscope, Bern, Switzerland.
- Veterinary Physiology, Vetsuisse Faculty, University of Bern, Bern, Switzerland.
- Veterinary Physiology, Vetsuisse Faculty, University of Bern, Bern, Switzerland.
MeSH Terms
- Adaptation, Physiological
- Administration, Intravenous / veterinary
- Adrenocorticotropic Hormone / administration & dosage
- Animals
- Cattle / blood
- Cattle / physiology
- Dairying
- Female
- Glucocorticoids / metabolism
- Hormones / administration & dosage
- Horses / blood
- Horses / physiology
- Hydrocortisone / analysis
- Hydrocortisone / blood
- Hypothalamo-Hypophyseal System / physiology
- Pituitary-Adrenal System / physiology
- Saliva / chemistry
- Specimen Handling / veterinary
References
- Alexander SL, Irvine CH. The effect of social stress on adrenal axis activity in horses: the importance of monitoring corticosteroid-binding globulin capacity.. J Endocrinol 1998 Jun;157(3):425-32.
- Bartalena L, Hammond GL, Farsetti A, Flink IL, Robbins J. Interleukin-6 inhibits corticosteroid-binding globulin synthesis by human hepatoblastoma-derived (Hep G2) cells.. Endocrinology 1993 Jul;133(1):291-6.
- Bousquet-Mélou A, Formentini E, Picard-Hagen N, Delage L, Laroute V, Toutain PL. The adrenocorticotropin stimulation test: contribution of a physiologically based model developed in horse for its interpretation in different pathophysiological situations encountered in man.. Endocrinology 2006 Sep;147(9):4281-91.
- Breuner CW, Delehanty B, Boonstra R. Evaluating stress in natural populations of vertebrates: total CORT is not good enough. Funct. Ecol. 2013;27:24–36.
- Breuner CW, Orchinik M. Plasma binding proteins as mediators of corticosteroid action in vertebrates.. J Endocrinol 2002 Oct;175(1):99-112.
- Brossaud J, Gatta B, Tabarin A, Corcuff JB. Different methods to estimate serum free cortisol: a comparison during cortisol tetracosactide testing.. Clin Chem Lab Med 2015 Aug;53(9):1367-73.
- Fureix C, Benhajali H, Henry S, Bruchet A, Prunier A, Ezzaouia M, Coste C, Hausberger M, Palme R, Jego P. Plasma cortisol and faecal cortisol metabolites concentrations in stereotypic and non-stereotypic horses: do stereotypic horses cope better with poor environmental conditions?. BMC Vet Res 2013 Jan 7;9:3.
- Gayrard V, Alvinerie M, Toutain PL. Interspecies variations of corticosteroid-binding globulin parameters.. Domest Anim Endocrinol 1996 Jan;13(1):35-45.
- Gross JJ, Zbinden RS, Dohme-Meier F, Bruckmaier RM. Adrenal cortex reactivity in dairy cows differs between lactational stages and between different feeding levels.. J Anim Physiol Anim Nutr (Berl) 2018 Feb;102(1):e309-e315.
- Hammond GL, Smith CL, Paterson NA, Sibbald WJ. A role for corticosteroid-binding globulin in delivery of cortisol to activated neutrophils.. J Clin Endocrinol Metab 1990 Jul;71(1):34-9.
- Hart KA, Barton MH, Ferguson DC, Berghaus R, Slovis NM, Heusner GL, Hurley DJ. Serum free cortisol fraction in healthy and septic neonatal foals.. J Vet Intern Med 2011 Mar-Apr;25(2):345-55.
- Hosoi K. Physiological role of aquaporin 5 in salivary glands.. Pflugers Arch 2016 Apr;468(4):519-39.
- Keremi B, Beck A, Fabian TK, Fabian G, Szabo G, Nagy A, Varga G. Stress and Salivary Glands.. Curr Pharm Des 2017 Oct 30;23(27):4057-4065.
- Levine A, Zagoory-Sharon O, Feldman R, Lewis JG, Weller A. Measuring cortisol in human psychobiological studies.. Physiol Behav 2007 Jan 30;90(1):43-53.
- Lewis JG, Lewis MG, Elder PA. An enzyme-linked immunosorbent assay for corticosteroid-binding globulin using monoclonal and polyclonal antibodies: decline in CBG following synthetic ACTH.. Clin Chim Acta 2003 Feb;328(1-2):121-8.
- Otovic P, Hutchinson E. Limits to using HPA axis activity as an indication of animal welfare.. ALTEX 2015;32(1):41-50.
- Peeters M, Sulon J, Beckers JF, Ledoux D, Vandenheede M. Comparison between blood serum and salivary cortisol concentrations in horses using an adrenocorticotropic hormone challenge.. Equine Vet J 2011 Jul;43(4):487-93.
- Proctor GB. The physiology of salivary secretion.. Periodontol 2000 2016 Feb;70(1):11-25.
- Scheidegger MD, Gerber V, Bruckmaier RM, van der Kolk JH, Burger D, Ramseyer A. Increased adrenocortical response to adrenocorticotropic hormone (ACTH) in sport horses with equine glandular gastric disease (EGGD).. Vet J 2017 Oct;228:7-12.
- Scheidegger MD, Gerber V, Ramseyer A, Schüpbach-Regula G, Bruckmaier RM, van der Kolk JH. Repeatability of the ACTH stimulation test as reflected by salivary cortisol response in healthy horses.. Domest Anim Endocrinol 2016 Oct;57:43-7.
- Schwinn AC, Knight CH, Bruckmaier RM, Gross JJ. Suitability of saliva cortisol as a biomarker for hypothalamic-pituitary-adrenal axis activation assessment, effects of feeding actions, and immunostimulatory challenges in dairy cows.. J Anim Sci 2016 Jun;94(6):2357-65.
- van der Kolk JH, Fouché N, Gross JJ, Gerber V, Bruckmaier RM. A comparison between the equine and bovine hypothalamus-pituitary-adrenocortical axis.. Domest Anim Endocrinol 2016 Jul;56 Suppl:S101-11.
- Verkerk GA, Macmillan KL, McLeay LM. Adrenal cortex response to adrenocorticotropic hormone in dairy cattle.. Domest Anim Endocrinol 1994 Jan;11(1):115-23.
- Vining RF, McGinley RA. The measurement of hormones in saliva: possibilities and pitfalls.. J Steroid Biochem 1987;27(1-3):81-94.
- Vining RF, McGinley RA, Maksvytis JJ, Ho KY. Salivary cortisol: a better measure of adrenal cortical function than serum cortisol.. Ann Clin Biochem 1983 Nov;20 (Pt 6):329-35.
- Yoshida C, Nakao T. Response of plasma cortisol and progesterone after ACTH challenge in ovariectomized lactating dairy cows.. J Reprod Dev 2005 Feb;51(1):99-107.
Citations
This article has been cited 7 times.- Nickles KR, Relling AE, Garcia-Guerra A, Fluharty FL, Parker AJ. Environmental stress during the last trimester of gestation in pregnant cows and its effect on offspring growth performance and response to glucose and adrenocorticotropic hormone. J Anim Sci 2023 Jan 3;101.
- Pinto G, Militello R, Amoresano A, Modesti PA, Modesti A, Luti S. Relationships between Sex and Adaptation to Physical Exercise in Young Athletes: A Pilot Study. Healthcare (Basel) 2022 Feb 11;10(2).
- Contreras-Aguilar MD, Henry S, Coste C, Tecles F, Escribano D, Cerón JJ, Hausberger M. Changes in Saliva Analytes Correlate with Horses' Behavioural Reactions to An Acute Stressor: A Pilot Study. Animals (Basel) 2019 Nov 18;9(11).
- Chen S, Wang J, Peng D, Li G, Chen J, Gu X. Exposure to heat-stress environment affects the physiology, circulation levels of cytokines, and microbiome in dairy cows. Sci Rep 2018 Oct 2;8(1):14606.
- Rachidi F, Wagner R, Fieseler H, Kaiser M, Müller H, Bittner-Schwerda L, Podpečan O, Mielenz N, Gottschalk J, Einspanier A, Möbius G, Starke A. Tears and saliva as alternative matrices for minimally invasive assessment of acute stress and pain in sheep. Front Vet Sci 2026;13:1719442.
- Briggs RK, Legako JF, Broadway PR, Carroll JA, Burdick Sanchez NC, Ineck NE, Smith ZK, Ramanathan R, Thornton KJ. Effects of Premortem Stress on Protein Expression, Steak Color, Oxidation, and Myofibrillar Fragmentation Index in the Longissimus Lumborum. Animals (Basel) 2024 Jul 25;14(15).
- Kern J, Jorgensen MW, Boerman JP, Erasmus M, Johnson JS, Pempek JA. Effect of repeated HPA axis stimulation on hair cortisol concentration, growth, and behavior in preweaned dairy cattle. J Anim Sci 2024 Jan 3;102.